ALBERT

Notes: Summary Radiation action occurs over a broad timescale which extends from the very early physical processes associated with energy absorption to the very late biological effects, such as carcinogenesis which may not become apparent until many years later. The various temporal stages of radiation action are classified and their interrelationships described. Experimental projects in cellular radiation chemistry, including pulse radiolysis, are discussed, together with some applications of the techniques in this general area. The paper also deals with some aspects of the oxygen effect in radiobiology and the mechanisms of its action. Various studies employing fast response techniques have been useful in verifying the role of fast free radical reactions in the oxygen effects and examples are given of some applications. Investigations with other hypoxic cell sensitizers, the electron affinic agents, are also briefly discussed, with an account of how studies of the timescale of radiation sensitization can be valuable in understanding mechanisms. Possible mechanisms of action of radiation sensitization by oxygen and other agents, including radical fixation and direct action processes, are considered in the light of evidence from some model systems.

Notes: Summary An analysis of primary processes in the formation of excess acentric fragments in human lymphocytes was carried out in experiments with 220 kV X-rays after acute exposure $$(\dot D = 50R/\min ,25 - 400R)$$ and fractionated exposure (340 R split into two equal fractions, separated by intervals between 50–360 min). Chromosome analyses occurred after conventional staining. Applying G-banding data from an acute X-irradiation experiment representative dose-effect curves for acentrics could be established which take into account one-break and two-break events in the formation of this aberration type. For the time dependent primary breaks necessary for the formation of two-break two-track acentrics a mean interaction time t ∼ = 102 min could be calculated. This is well in line with the corresponding time t ∼ = 110 min for dicentrics. The distribution of acentrics among cells shows the phenomenon of overdispersion.

Notes: Summary The quantum yields of fluorescence and phosphorescence and the triplet lifetimes were determined for 29 phenothiazine derivatives; theφ p values are varying from 0.2 to 1. The irradiation of phenothiazine derivatives in aerated solutions yields from the triplet state to the formation of singlet oxygen and more especially of superoxide ions and cation-radicals characteristic of the dye. Relative values of the formation rate were determined for these two mechanisms. Production of cation-radicals was correlated with phototoxicity in vivo. Chlorination enhances the two phenomena and acetylation reduces to nothing. A maximum value was estimated for the quantum yield of photoionization.

Notes: Summary The potential of electromagnetic radiation and ultrasound for generating hyperthermia in tissues is discussed. Electrical properties, propagation parameters for electromagnetic and ultrasonic radiation and reflection problems yield limitations on most suitable frequency choices. Considerable insight has been gained in electromagnetic induced heat deposition patterns for the case of whole body irradiation and for local irradiations which can cause hot spot type of heating patterns. Pertinent results are compared and indicate that frequencies near 1000 MHz may be optimal for the electromagnetic case. But RF-frequencies using frequencies sufficiently low to reduce the magnetically induced term provide probably greater reproducibility. Finally recent work on mm-wave therapy and diagnosis is indicated. Emphasis is on the comparative merits of the various possible approaches.

Notes: Summary The paper presents results of measurements made on cereals and composite meal samples collected from Bombay market for their lead-210 content. The details of sampling and analytical chemistry procedures are also given. The Pb-210 contents of most of these samples were in the range of 1–5 pCi/kg of cereals samples. The concentrations in composite meal samples were mostly in the range of 1–3.5 pCi of210Pb per composite meal. The assessment of daily intake of this isotope through food-stuffs has been made.

Notes: Summary The survival of UV irradiated phage lambda was increased on X-irradiatedE. coli K-12 host cells over that on unirradiated cells. The frequency of c mutants among the surviving phages was to a similar extent increased by the X-ray exposure of the host cells as by UV light. This W-reactivation of phage lambda occurred inuvrA, polA, andrecB mutants besides the wild type at about equal X-ray doses, however, at a reduced reactivation efficiency compared with the wild type. W-reactivation was undetectable inrecA mutants. While maximal UV induced W-reactivation occurred 30 min after irradiation, the maximal X-ray induced reactivation was found immediately after irradiation. Chloramphenicol (100 µg/ml) and nitrofurantoin (50 µg/ml) inhibited W-reactivation of phage lambda if added before irradiation of the host cells, indicating the necessity of protein synthesis for W-reactivation.

Notes: Summary Excision repair was studied in normal human and ataxia telangiectasia (AT) cells proficient in repair of UV and its mimetic chemicals, and in xeroderma pigmentosum group C (XP C) cells (deficient in repair of UV and its mimetics), after treatment with several combinations of chemical carcinogens, by the photolysis of bromodeoxyuridine incorporated into parental DNA during repair. Results indicate that repair was additive in AT, and XP C cells treated with N-acetoxy-2-acetylaminofluorene (AAAF) plus ethyl methanesulfonate (EMS) or methyl methanesulfonate (MMS) indicating that there are different rate limiting steps for removal of both types of damage. Data on the combinations of 4-nitroquinoline 1-oxide (4NQO) plus MMS or EMS are difficult to interpret, but they do not indicate inhibition of DNA repair.

Notes: Summary The numerical relationship between radiation-induced chromosome aberrations in humanG 0 lymphocytes and reproductive lethality of human bone-marrow lymphocytes is analysed within a large LET interval. The comparison is based upon the evaluation of the coefficient α of the linear component of the corresponding dose-effect-relation for the frequency of cells without aberrations and for the frequency of surviving cells respectively. The good correlation between these coefficients over a large LET interval supports the hypothesis that structural chromosome aberrations and reproductive cell death both result from the same gross chromatin damage.

Notes: Summary Rat liver homogenate has been submitted to pulsed electric fields at different intensities and exposition times. Among the paramagnetic species present in the samples only the mitochondria free radical is affected by pulsation, as revealed by electron spin resonance spectroscopy. In parallel a variation in the respiratory activity of mitochondria is registered.

Notes: Summary Electrooxidation and electroreduction ofγ- and u.v.-irradiated DNA were studied by means of differential pulse voltammetry at the graphite electrode and differential pulse polarography at the dropping mercury electrode. Two separated voltammetric oxidation peaks G and A were used for monitoring conformational changes in guanine - cytosine (GC) and adenine - thymine (AT) pairs respectively in irradiated double-stranded (ds) DNA. Pulse-polarography reduction peak III was used for detection of denatured DNA in the irradiated samples of ds DNA. It was found that the heights of peaks G and A of ds DNA did not change with the radiation dose after relatively low doses ofγ- and u.v.-radiations (up to ca. 40 krads and 1 × 104 Jm−2, respectively), when no single-stranded (ss) DNA was detected in the irradiated DNA samples. After higher doses of radiation the occurrence of ss DNA or ss segments in the irradiated samples of ds DNA was accompanied by an increase of peaks G and A; however, peak A grew more rapidly with the increasing dose than peak G. It was concluded that the results obtained support the assumption, according to which regions of ds DNA rich in AT pairs are more susceptible to denaturation caused byγ- and u.v.-radiations.

Notes: Summary The feasibility, and the biophysical and engineering concepts underlying the use of electromagnetic energy and ultrasound for production of deep, local hyperthermia are discussed. Focused ultrasound currently is the only modality that can be used for producing controllable levels of hyperthermia localized to deep seated tumors, non-invasively and safely. The ultrasonic focus needs to moved within the tissues around the periphery of the tumor to achieve uniform temperature distributions.

Notes: Summary The physical and mechanical parameters to be considered when contemplating hyperthermia as a cancer treatment modality are discussed. These parameters include heat field size, uniformity of heating, method of hyperthermic production, selection of energy, heat flow, warm-up period and thermometry.

Notes: Summary At five stages of gestation, mice were exposed dorsally to ultrasonic irradiation at 1 W/cm2 (spatial and temporal average), 2 MHz, and 34 and 37° C (temperature at beginning of exposure). The results indicated that ultrasonic exposure up to at least 100 s is not hazardous to a pregnant mouse or its offspring in utero under the conditions of our experiment. Thresholds for both undesirable and lethal effects on the dam and its embryos or fetuses appeared between 100 and 200 s. Temperature rises in the uterus to more than 40° C and similarity of results obtained with continuous-wave and burst modes of irradiation suggest a thermal mechanism as one cause of these effects. Preliminary conclusions are that thresholds for both tissue damage to the dam and deleterious effects on pregnancy were similar; however, they occurred at spatial average intensity and exposure levels far in excess of those used in clinical diagnostic medicine.

Notes: Summary Wild type diploid yeast, Saccharomyces cerevisiae strain 211, was subjected to 250 kV X-rays or 50° C heat treatment for 30 min or to a combination of both. X-ray exposure took place either in air or in nitrogen. Cell number, percentage of budding cells and cell cycle progression was followed for up to 12 h post irradiation. The distribution of cell cycle stages was determined by flow cytofluorometry. All treatments cause a retardation of cell division rate. Hyperthermia leads mainly to a lengthening of G1, whereas X-rays arrest the cells reversibly in G2. The effect of the combined treatment appears to be merely additive. No selective action of hyperthermia on hypoxic cells was found.

Notes: Summary Pregnant mice were exposed to ultrasound (continuous wave, 2 MHz) on Day 8 of gestation to determine effects on the progeny. The most significant finding was a decrease in mean uterine weight of the female progeny. The thresholds for this effect were 140 s at 0.5 W/cm2 and 60 s at 1 W/cm2, which were below the thresholds previously reported for other effects in mice. We suggest that this indicates a delay or impairment of maturation of the mice exposed in utero. Exposure of the dams to spatial average intensity of 1 W/cm2 for 40 and 60 s had no effect on body weight of the progeny, compared with sham-treated controls. In this experiment the body weights of progeny from sham-treated controls were significantly lower than those from untreated controls on Days 10, 17, and 25 of age. After exposure in utero to 0.5 W/cm2 for 180 s, statistically significant decreases in mean body weights of the neonates were observed, but only on Day 25 of age, in both sexes compared with sham-treated controls. At necropsy at Day 25 of age, neonatal organ weights relative to body weights were not significantly affected for the thymus in either sex or for the seminal vesicles and testes in comparison with sham-treated controls.

Notes: Summary Properties of calf thymus DNA were investigated after treatment with the pesticides malathion (0,0-dimethyl-S-(1,2-bis ethoxycarbonyl ethyl)dithiophosphate) and DDVP (0,0-dimethyl-0-(2,2 dichlorovinyl)phosphate) in vitro by means of derivative (differential) pulse polarography (DPP), thermal denaturation curves recorded spectrophotometrically (Tm), viscometric measurements, and chromatography on the hydroxyapatite column. Changes in the properties of DNA were observed by means of DPP after only a few hours incubation with the pesticides, whereas the other methods did not detect any changes even after 48 h. The results obtained by DPP indicate that single-stranded segments and thermolabile regions are formed in DNA due to the action of the pesticides. This behaviour could perhaps be a consequence of guanine alkylation followed by depurination and chain scission at elevated temperatures. Malathion and DDVP differ in the kinetics of reaction with double-helical DNA. DDVP is more reactive and its action is also manifested after 72 h in changes in viscosity, Tm, and chromatographic behaviour on the hydroxyapatite column. The changes induced by malathion were, under identical conditions, not detectable by these methods.

Notes: Summary Analyses of structural aberrations of chromosomes and of the body burden of lead-210 were carried out in a group of workers occupationally exposed to chemical pollutants and low doses of ionizing radiation during a technological process in which coal is used as fuel. A parallel study was performed in a control group of workers. In the exposed group the percentage of chromatid and chromosome aberrations and the results of radiochemical analyses were higher than in the control group.

Notes: Summary Erythropoietic changes were observed, measured by59Fe-uptake into red blood cells, and on radioiron turnover from blood plasma, at different time intervals (2–64 days) after treating adult female mice with varying activities of90Sr-90Y. Activities of 2.5 or 5.0 µCi radiostrontium per animal lead to a depression at time intervals of two and four days, at longer periods there was an overshoot. With activities of 0.5 or 1.0 µCi radiostrontium disturbances in the radioiron uptake are still observed, although these effects are not as pronounced as in experiments with higher burdens. In comparison with results obtained in experiments in which the plasma59Fe-turnover was applied, even with an activity of 5 µCi radiostrontium per mouse, no deviation as against the untreated controls was detected.

Notes: Summary Malate synthase was investigated by the small-angle X-ray scattering technique in aqueous solution. Measurements extending for several hours revealed a continuous increase of the intensity in the innermost portion of the scattering curve. There is clear evidence that this increase was caused by an X-ray induced aggregation of enzyme particles during the performance of the small-angle X-ray scattering experiment. The monitoring of the aggregation process in situ by means of small-angle X-ray scattering led to a model of the way how the aggregation might proceed. The analysis of the scattering curves of malate synthase taken at various stages of aggregation established the retention of the thickness factor of the native enzyme and the occurrence of one and later on of two cross-section factors. The process of aggregation was also reflected by the increase of extension of the distance distribution function. According to these results, the first step of aggregation might be a linear side-by-side association of the oblate enzyme particles, a process which is followed by a twodimensional aggregation. An aggregation in the third dimension was not observed during the time covered by our experiment. The predominance of aggregation in only one or two dimensions was corroborated by comparison of appropriate theoretical scattering curves with the experimental curves. The theoretical scattering curves for this comparison were obtained by averaging over the properly weighted scattering curves calculated for various species of hypothetical aggregates. The time dependence of the apparent mean radius of gyration was used to compare the aggregation of enzyme samples that were irradiated under different experimental conditions. It turned out that by addition of dithiothreitol to the enzyme solutions as well as in the presence of the substrates (acetyl-CoA, glyoxylate) or of a substrate analogue (pyruvate) or of ethanol the rate of aggregation is reduced. Enzymic activity was found to decrease about exponentially with increasing X-ray dose. The presence of dithiothreitol or of the substrate glyoxylate or of the substrate analogue pyruvate protects the enzyme against X-ray induced inactivation. The substrate acetyl-CoA does not exhibit a comparable protective effect against inactivation. Measurements of enzymic activity and small-angle X-ray scattering on samples, which had been X-irradiated with a defined dose prior to the measurements, established two different series of efficiency for the protection of the enzyme against aggregation (pyruvate 〉 glyoxylate 〉 acetyl-CoA) and inactivation (glyoxylate 〉 pyruvate $$ 〉 〉 $$ acetyl-CoA). The results showed that there is no direct relation between the extent of aggregation and the loss of enzymic activity.

Notes: Summary For the radioiodine isotopes I-123, I-125, I-131, and I-132 the mean tissue dose and local dose distribution in the epithelial cells of a follicle have been calculated and compared to each other. Moreover, dose factors have been estimated for I-131 as a function of age considering age-dependent ingestion (milk consumption) and inhalation rates. Thereby, besides age-dependent biological half-times and thyroid masses, the thyroidal iodine uptake was assumed to be independent from age and taken to be about 1.7 the normal for an insufficient dictary iodine intake as in the Federal Republic of Germany.

Notes: Summary Declining yields of radiation-induced dicentric chromosomes in human G0 lymphocytes were observed in split-dose experiments with time intervals varied up to 8 h. In agreement with microdosimetric intratrack-intertrack interaction models, only the dose-squared yield component was reduced and approached an asymptotic value equal to one half of the corresponding single exposure yield. For 150 kV X-rays and 13 MeV electrons, at total doses up to 6 Gy, the time constantτ of the approximately exponential decline was practically dose- and quality-independent within a range of 100–180 min. For 10 kV X-rays, in the presence of a dominant linear yield component, only a small split-dose effect, but with a consistentτ-value, was observed for a total dose of 5 Gy. Sinceτ can be interpreted as the mean life time of “primary lesions” in chromatin fibres, its independence from absorbed dose and radiation quality means that radiation damage of the split-dose recovery mechanism can be excluded for doses up to 6 Gy. By correlating the observed split-dose reduction of the acentric fragment yield to the reduction of the dicentric yield, (1.64 ± 0.03) acentrics/dicentric for 150 kV X-rays and (1.51 ± 0.11) acentrics/dicentric for 13 MeV electrons were obtained. Acentrics formed in the course of dicentric formation as well as in other binary interactions of “primary lesions” are represented in these ratios. Post-irradiation recovery during time intervals between irradiation and cell stimulation up to 24 h did not occur. The relations to comparable results in cell lethality experiments are discussed, and a hypothesis of “fast” and “slow” binary interactions of “primary lesions” is put forward.

Notes: Summary The varying sensitivity to radiation in the different phases of the cell cycle was investigated using L-929 cells of the mouse. The cells were synchronized by mechanical selection of mitotic cells. The synchronous populations were X-irradiated with a single dose of 10 Gy in the middle of the G1-phase, at the G1/S-transition or in the middle of the S-phase, respectively. The radiation effect was determined in 2 h intervals a) by14C-TdR incorporation (IT) into the DNA, b) by autoradiography (AR), c) by flow cytometry (FCM). The incorporation rate decreased in all three cases, but the reasons appeared to be different, as can be derived from FCM and AR data: After irradiation in G1, a fraction of cells was prevented from entering S-phase, after irradiation at G1/S a proportion of cells was blocked in the S-phase, and after irradiation in S, DNA synthesis rate was reduced. As a consequence of these effects, the mean transition time through S-phase increased. The G2 blocks, obtained after irradiation at the three stages of the cycle were also different: Cells irradiated in G1 are partly released from the block after 10 h. Irradiation at G1/S caused a persisting accumulation of 50% of the cells in G2, and for irradiation in S more than 80% of the cells were arrested in G2.

Notes: Summary Thorotrast is a X-ray contrast medium which has been used in the ears 1930–1950. It is hardly ever eliminated from the body and is stored in the organs of the reticulohistiocytic system (RHS). Since Thorotrast contains all radionuclides of the thorium decay chain, the effect of internal irradiation by these radionuclides can be investigated in the so called “Thorotrast patients”. It is the purpose of this study to determine the radiation dose absorbed by the lymphocytes of the peripheral blood of these persons, and to correlate it with their chromosome aberration rate. Part I of the paper describes the physical aspects of dose evaluation. The chromosome aberration rates of Thorotrast patients were subjected to a repeated statistical test. They show a logarithmic normal distribution at a mean value of about seven dicentric chromosomes per 100 cells. The corresponding dose has to be determined. The method for evaluating size and distribution of Thorotrast conglomerates in the examined tissue is demonstrated, and the function and resolution power of the applied “texture analysing system” (TAS) is described. Size-distributions of Thorotrast conglomerates of lymph nodes from the neck, the lung and from the lower aorta (bifurcatio) are given. In the lymphatic system more than 90% of the absorbed dose in tissue is due toα-particles. The computation method of calculating the self-absorption ofα-particles in the conglomerates and of calculating the annual doses in the lymph nodes is described. The values lie between 135 and 1200 rad/year. The contribution to irradiation from outside the lymphatic system can be neglected. The method of dose determination is discussed and compared with microdosimetric methods. With these methods, the dose of a lymphocyte caused by one hit of anα-particle lies between 80 and 920 rad. An energy dissipation does not take place and the total energy emitted acts on the lymphocytes thus inducing chromosome aberrations.

Notes: Summary The biological effect ofα-radiation, which has been examined in this investigation, is the occurence of chromosome aberrations in lymphocytes from the peripheral blood of Thorotrast patients. To set up a dose-effect relationship, it is necessary to estimate the absorbed dose of a single lymphocyte found in a blood sample. Then it would be possible to use chromosome aberrations of lymphocytes from peripheral blood as an indicator for estimating the effective radiation dose. The physical aspects of this investigation have been described in part I of this paper. In part II, biomedical considerations are described and discussed. The irradiation of the lymphocytes takes place in the whole lymphatic system, but the lymph node could have been used as a model for the lymphatic system. Based on the evaluation of size and distribution of Thorotrast conglomerates, the average annual dose in different structures of the lymph node has been determined. The Thorotrast content in lymph nodes depends on the region of the body from where the lymph nodes originate. It has been tried to compile the distribution of the lymph nodes in the different regions of the body. Annual doses have been calculated in these different regions in order to find a representative value for the whole body. The values describing the kinetics of the lymphocytes in the body have been used to convert the annual dose in lymph nodes into the dose of a lymphocyte found in a sample of peripheral blood. It is pointed out that the calculated dose of the lymphocytes, being 250 rad, is an estimation of an upper value. The lymphocytes are “in vivo” irradiated by the Thorotrast, but most of the calibrations used for biological dosimetry are refered to as “in vitro” experiments. The discrepancy between “in vivo” and “in vitro” results are discussed in the findings of this study and in other results.

Notes: Summary The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a “Rossi type” proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 μm diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behaviour as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8–31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.

Notes: Summary The effect of model compounds comprising alcohols and paraffins on the radiation sensitivity ofB. pumilus spores has been carried out with the aim of understanding the radiation-induced inactivation of microorganisms when suspended in non-aqueous medium. This study is a prerequisite to the undertaking of radiation sterilization of non-aqueous pharmaceuticals. Spores ofB. pumilus E601 mounted on kaolin powder were suspended in the appropriate organic agent and gamma irradiated under oxic conditions. Spores suspended in paraffins displayed increased radiation response over that for aerated buffered suspensions. Values of inactivation constant ranged between 2× and 5× that for buffer. Less pronounced modification of response was obtained for the alcohols. The results reveal a marked tendency for response to increase with decreasing polarity of the suspending fluid. The partial miscibility of the alcohols in water enabled the examining of the transition from the response characteristic of aerated buffered suspensions to those of the spores in pure organic liquids.

Notes: Summary Non-linear mechanical response of viscoelastic strain responding media to high amplitude stress-strain is examined from a phenomenological point of view and found to lead to results compatible with empirical observations of high intensity ultrasound irradiation of brain, liver, and eye lens tissues. The proposed hysteresis model provides for most of the observed dependencies such as an intensity dependent absorption coefficient, an absorption coefficient increasing linearly with frequency, and a dispersionless velocity of ultrasound in soft tissues (excluding lung). The non-linear compliance of tissues further predicts production of half-harmonic signals even in the absence of cavitation.

Notes: Summary The radiosensitivity of hemopoietic stem cells isolated from infant mice (6 or 9 days of life), of infant preirradiated mice (exposed to 126 rad on day 6 and assayed at day 9 of life) and of adult C57/B1 mice was assayed on the basis of their capacity to form spleen colonies and to incorporate iododeoxyuridine after transplantation into heavily irradiated hosts. Stem cells of infant non-irradiated mice have a D0 of 115 rad compared to 72 rad for adult mice whereas the D0 of preirradiated infant mice has diminished to 80 rad. No significant difference in D0 was seen between spleen and bone marrow cells or between total cells and cells not sensitive to3H-thymidine. It is postulated that this sensitization of stem cells caused by a preirradiation is responsible for the greater mortality of infant mice after fractionated exposure compared to a single one.

Notes: Summary A one-dimensional and a three-dimensional computer model have been built in order to study the importance of blood flow and ultrasonic absorption in tissues during local hyperthermia. The decreased blood flow in the interior of certain tumours and possibly the increased ultrasonic absorption of the malignant tissue in some cases may cause selectively higher temperatures inside the tumours though the heat input is the same as in the surrounding tissues. Also, the vasodilation of blood vessels in normal tissues as a response to heat causes a therapeutically useful temperature difference. These blood flow differences can lead to enhanced effects during sonication to produce hyperthermia in the tumour. The inhomogenity of blood flow in the tumour causes a non-uniform temperature distribution leaving the well-perfused cells in the advancing front at a much lower temperature than the cells in the necrotic centre. Thus, the combination of local hyperthermia with radio-and chemotherapy seems to offer the most attractive means of destroying malignant tissue.

Notes: Summary Chromosome analyses were carried out in lymphocytes of 32 workers occupationally exposed for more than 20 years to 50 Hz alternating electric and magnetic fields in 380 kV switchyards. As compared with a control group of 22 workers of similar age and occupation but without field exposure neither the yields of structural chromosome changes nor the SCE-frequencies were increased. The difference of cytogenetic data after occupational exposure to ionizing radiation is discussed.

Notes: Summary Denatured calf-thymus DNA was X-irradiated, coupled to methylated bovine serum albumin and injected into rabbits to study the possible formation of specific antibodies. The serological activity was tested by a modified Farr-test, a micro complement binding reaction and by caesium chloride isopycnic ultracentrifugation. It was found with all assays that the immunological reaction was mainly due to unspecific DNA-binding and only a very small amount to radiation products. It seems, therefore, that this approach is not suitable for the analytical investigation of DNA damage produced by ionizing radiation.

Notes: Summary Although extension of the time period during which a given dose of radiation is administered commonly reduces effectiveness, there are well established instances where the reverse is true. Theoretical considerations are presented which relate reduction or enhancement to the shape of the dose-effect curve. While in many instances these changes of sensitivity may be due to intracellular processes it appears that in the case of carcinogenesis by low doses of neutrons, time dependent intercellular action must be involved.

Notes: Summary The short term effects on the free macrophage population in the mouse lung, following inhalation of thulium-170 oxide, have been studied, with a view to using the system as a model with which to compare the short term effects of inhomogeneous alpha irradiation. The clearance and distribution of thulium-170 was followed up to 44 days post inhalation. The mice had an initial lung burden (± SE) of 6.7 ± 0.5 µCi170Tm/g of lung and the pattern of removal of this could be described by a single exponential of half time 31 ± 4 days. This exposure resulted in a uniform dose of about 24 Gy to the lung. The macrophage population was studied by counting cells lavaged from the lungs at intervals over the period of the experiment. The lung burden of170Tm2O3 was found to decrease the free macrophage numbers by about a factor of 2 in 14 days with some slight recovery at 6 weeks post inhalation. It was found that nearly 50% of the activity in the lung lobes was removed by the lavages and that this fraction remained constant throughout.

Notes: Summary Exposure of normal human fibroblasts (F107) in stationary phase to γ radiation inhibited the appearance of induced ornithine decarboxylase (ODC) activity. Skin fibroblasts derived from two ataxia telangiectasia (AT) patients (F184 and F182) displayed a similar response. The level of DNA repair synthesis was also similar in the three cell strains. Fibroblasts from another apparently normal donor (F196) were very sensitive to inhibition of induced ODC activity by γ radiation and were also deficient in radiation-induced DNA repair synthesis. However, the two strains derived from normal donors displayed the same degree of cellular sensitivity towards X-rays, whereas the two AT strains showed the typical hypersensitivity to the cytotoxic effect of X-irradiation. The results suggest a possible correlation between the inhibition of induced ODC activity by γ radiation and the extent of DNA repair synthesis at high radiation doses, but there is no correlation between these two parameters and cellular survival at low radiation doses.

Notes: Summary The regenerative ability of haemopoietic organs during combined radiation injuries has not been adequately investigated. Interactions among individual factors can critically influence the processes involved in haemopoietic recovery. An overview of radiation injuries is given, and a concept towards a hypothetical mode of action at the cellular level is presented. The influence which interacting factors can have on the concentration of pluripotential haemopoietic stem cells (HSC) is demonstrated by results from an initial experiment. The importance of synergistic and antagonistic reactions is emphasised and commented upon.

Notes: Summary The biological effects of microwaves in the hyperfrequency range, 9.4 GHz, 17 GHz, and 70–75 GHz were investigated in bacteria and yeast. At power densities below 60 mW/cm2 and SAR values not exceeding 28 mW/g no significant effects on survival of repair competent and deficient strains were observed inEscherichia coli andSaccharomyces cerevisiae. In addition, microwaves of 17 GHz did not induce mutations inE. coli B/r WP2trp − uvr − above the spontaneous level, and the induction of nuclear reversions, cytoplasmic “petite” mutations and mitotic recombination as well as the efficiency of sporulation was not affected in yeast.

Notes: Summary Bacteria of the typeE. coli K12 have been treated in experiments using high-voltage pulses of short time (µs) as a killing agent. The role of different experimental parameters has been studied: kind of electrolyte, concentration, length of pulses, field strength, pH and temperature. Electrolytes with bivalent cations were found to reduce the lethal action. The relative rate of killed bacteria was shown to be mainly governed by the field strength and the treatment time, which is defined by the product of pulse number and decay time constant. From the obtained results a function has been developed which enables the precalculation of the killing rate forE. coli, provided that certain limits of experimental conditions are considered. No correlation between the applied electric energy and the lethal effect could be found.

Notes: Summary A simple theoretical model is proposed for estimating the differential contribution of ionization and excitation to the lethal effect of ionizing radiation. Numerical results were obtained on the basis of published experimental data on the ability of bacterial cellsEscherichia coli to undergo photoreactivation of radiation-induced damage. It was shown that inactivation by excitation may be highly significant for UV-hypersensitive cells capable of photoreactivation; inactivation by excitation increased with the energy of ionizing radiation and the volume of irradiated suspensions. The data are in qualitative agreement with the assumption of a possible contribution of the UV-component of Čerenkov radiation to the formation of excitations responsible for the lethal effect and the phenomenon of photoreactivation after ionizing radiation. Some predictions from the model are discussed.

Notes: Summary Reduction of the four disulfide bonds and further carboxymethylation of lysozyme followed by its reaction with CNBr brings about L-I, (aa 1–12) and L-II-III (aa 13–129) peptides. When breaking the polypeptidic chain by CNBr action and freeing the peptides formed through S-S bonds reduction and carboxymethylation three peptides are obtained corresponding to L-I (aa 1–12), L-II (aa 13–105) and L-III (aa 106–129). L-II-III, L-III and L-II peptides were separately subjected to photo-oxidation in presence of riboflavin, in 0.05 M phosphate buffer, pH 7.0. The kinetic analysis of Trp photo-oxidation in L-II-III peptides shows that these residues keep, to a great extent, the degree of exposition they had in native lysozyme. L-II peptide also presents Trp residues with a different degree of exposition. Presence of Tyr photo-oxidation in L-II and L-II-III peptides - what does not take place in native lysozyme - suggests a relationship between photo-oxidation selectivity and the degree of exposition of certain amino acid residues in spatial configuration.

Notes: Summary The effects on cell survival of maintaining bone marrow cells (CFU-S) in situ following irradiation and before assay by transplantation was investigated. When the CFU-S cells are maintained in situ following irradiation survival drops and plateaus at about 9 h post-irradiation. Evidence is presented that this decrease in survival may be due to potentially lethal damage repair (PLD) inhibition caused by post-irradiation in situ holding. This effect on PLD repair is different than that usually found in cells in vitro and in vivo tumors in that it mainly alters the shoulder rather than the slope of the survival curve of CFU-S cells. It is different than PLDR found in vivo for normal mammary and thyroid gland epithelial cells because in situ holding decreases rather than increases the survival of CFU-S cells. Evidence is also presented that the radiation survival curve for in situ bone marrow cells (CFU-S) may not have a shoulder.

Notes: Summary Lung cancer induction is commonly regarded as the most important somatic risk arising from the inhalation of radon and its decay products. Relating carcinogenesis to radiation exposure needs a detailed knowledge of the cellular dose distribution in the human respiratory tract. Different dosimetric models have been developed for the determination of cellular doses, particularly for the basal cells of the bronchial epithelium which are considered as the critical cells for lung cancer induction. Part I of the paper describes the influence of various environmental as well as anatomical and physiological factors on the resulting dose. Significant inter- as well as intra-subject variabilities of structural components of the human lung, respiration characteristics and clearance mechanisms demonstrate the necessity of applying stochastic models in lung dosimetry.

Notes: Summary Lung dose calculations for inhaled radon decay products presented in part I have revealed that mean basal cell doses are significantly dependent on various personal and environmental factors. Whereas these macroscopic dosimetric methods have been applied with great success to radiation protection problems, the interpretation of radiobiological effects, such as lung cancer incidence, needs some refinement of these methods. Energy deposition at the microscopic level as the physical input quantity and radiation carcinogenesis as the biological endpoint are by nature stochastic processes. Therefore, a microdosimetric model was developed taking into consideration the randomness of physical and biological parameters involved. Part II of the paper presents results on specific energy distributions in lung cells, demonstrating that single event density distributions together with the number of cells receiving single hits represent more appropriate parameters than mean radiation doses.

Notes: Summary Turkey sperm were exposed to 2.45 GHz microwave radiation in a temperature controlled waveguide apparatus. Temperature was maintained at 40.0 ± 0.5° C. The sperm were exposed for 30 min to a specific absorption rate (SAR) of 1, 10, or 50 mW/g. Before and following microwave exposure the following parameters were examined: percentage viability, percentage abnormal sperm, and release of the enzymes lactate hydrogenase (LDH) and glutamic oxalic transaminase (GOT). These parameters were not altered significantly by microwave exposure under the conditions tested.

Notes: Summary Plant water potential, osmotic potential, stomatal resistance, leaf temperature, soil temperature, height, dry weight, and nutrient composition of winter wheat (Triticum aestivum L. em. Thell. ‘Osage’) grown with electromagnets 10 cm long were measured to determine the effect of magnets on water relations, temperature, and growth. Plants grew in 15-cm diameter pots in a growth room for 44 days with the magnets, which had 0, 5, 15, 25, 50, 125, or 250 ampere-turns. Plants grown with few ampere-turns (5–25) had higher water and osmotic potentials, lower stomatal resistances, were taller, had a higher dry weight, and a higher nitrogen concentration than control plants or plants grown with many ampere-turns (250). Leaf and soil temperatures of controls tended to be less than those of plants and soil with magnets. Calculations showed that magnets with 5–25 ampere-turns and 50–250 ampere-turns generated 0.86 and 0.43 cal/s, respectively. The latter value agreed with the measured increase in temperature (0.5° C) for soil with 250 ampere-turns. The data indicated that the increased height and dry weight of plants with 5–25 ampere-turns were due to soil heating caused by the magnets and heat produced by the 50–250 ampere-turns was not enough to stimulate growth.

Notes: Summary Experimental and clinical data on the four R's in fractionated radiotherapy are reviewed. The clinical importance of redistribution has not been proven in the experiment yet. On reoxygenation no unequivocal data in human cancer exists and a lot of variability in rodent tumours. Repair and regeneration are the most important of the four R's in fractionated radiotherapy. The presented experimental and clinical evidence suggests a differential response between tumour and late responding normal tissues with regard to these two R's. Tumours appear to have, in general, a smaller capacity for repairing sublethal radiation damage but a higher capacity for repopulation than late responding normal tissues.

Notes: Summary Man takes up nitrite in a considerable amount. Effects of nitrite on DNA have been reported; therefore, interaction between nitrite and radiation might be possible. Preimplantation mouse embryos in vitro were treated with a combination of sodium nitrite (1 mM or 2.5 mM) and X-rays (0.94 Gy) in order to obtain some information whether radiation risk is influenced by the presence of nitrite. The microscopic visible development up to 144 h post conceptionem (h p.c.), the number of cell nuclei, and the number of micronuclei were determined. None of the experimental results gives any indication that radiation risk is influenced by nitrite. All effects after combined treatment correspond to the sum of the single effects.

Notes: Summary Survival and G2 delay following exposure to either60Cobalt-γ-rays or241Americium-α-paticles were studied in eight mammalian cell lines of human and animal origin including human fibroblasts from normal individuals and from patients with Ataxia telangiectasia or Fanconi's anemia. For both endpoints the effectiveness of alpha particles was greater as compared toγ-rays. RBE values for G2 delay (4.6–9.2) were in general comparable to RBE values derived from initial slopes of survival curves (RBE α ) but higher compared to the ratio of mean inactivation doses $$\left( {RB_{\bar DML} } \right)$$ . Ataxia cells were particularly sensitive to cell killing byγ-irradiation (D37 = 0.57 Gy), however, showed average sensitivity toα-particles of high LET (D37 = 0.30 Gy). With the exception of Ataxia cells, cell killing and G2 delay seem to be related processes if individual cell cycle parameters are taken into account.

Notes: Summary Nonsulfur purple photosynthetic bacteria,Rhodopseudomonas spheroides cells grown aerobically in the dark were incubated with medium containing tritiated water (THO) under growth and no-growth conditions. R value defined as the ratio of specific activity (T/H) of tritium (T) incorporated into cell materials to T in medium was about 0.5 in growing cells and 0.2 in nongrowing cells regardless of THO-concentration in medium. From the fractionation of these lyophilized cells by modified Schneider method, the distribution of volatile T (i.e., exchangeable T) in cold perchloric acid (PCA)-soluble fraction, nonexchangeable T of small molecules in cold PCA- and ether-ethanol-soluble fractions and nonexchangeable T of macromolecules in hot PCA- and alkali-soluble fractions was 16 : 17 : 67 in growing cells and 38 : 24 : 38 in nongrowing cells. Moreover, the nucleic acids were extracted by phenol method from the cells incubated with THO and fractionated on methylated albumin-coated column chromatography. R value of nonexchangeable H in DNA, sRNA, and rRNA was 0.4–0.6 in growing cells and 0.06–0.13 in nongrowing cells. R value of nonexchangeable H in ribo- and deoxyribo-mononucleotides hydrolyzed by treatment with either KOH or DNase and phosphodiesterase was 0.38–0.84 in growing cells. Average R value of nonexchangeable H in nucleic acids and these mononucleotides in growing cells were similar to that of total H in the lyophilized cells. From the study of retention of T in the cells, radioactivity of T of long-lived component decreased at the biological half life of 69 h in nongrowing cells and at rate of 0.4n (n: number of cell division) in growing cells. The retention of bound T in nucleic acids of nongrowing cells was considerable, i.e., 100, 78, and 86% remaining after 16 h in DNA, sRNA, and rRNA, respectively, for 76% in the overall cells. Decrease of activity of nonexchangeable T bound to DNA in nongrowing cells was expected only the cell death.

Notes: Summary To investigate whether residual radiation damage in hematopoietic tissue is measurable in situ by a change in cell turnover, the retention of the thymidine analogue 5-(125-I)iodo-2′-deoxyuridine (125-IUdR) following incorporation into DNA of cells in bone marrow and spleen of mice was measured 35 days after 0–500 rad whole body gamma irradiation. In the bone marrow a rapid and a slow turnover component of 125-IUdR retention were found. Both components were almost identical for unirradiated and irradiated mice. In the spleen the 125-IUdR retention curves exhibited three components with increasingly prolonged half-times. In the second component the half-time was longer in irradiated than in unirradiated mice. This was dose-dependent. The increased half-time of 125-IUdR retention in irradiated spleens may be caused by direct cellular damage of long-lived cells (lymphocytes, early hematopoietic progenitor cells) or/and by diminished stimulation of proliferation by microenvironmental or long-range factors.

Notes: Summary Chinese hamster V79 cells in log-phase were exposed daily to 0.6 Gy ofγ radiation for 3–6 months. After such an exposure the population doubling time increased from 10 to 15 h. When irradiation was discontinued doubling time gradually decreased. Cell survival following acute radiation dose of the low-level irradiated cells remained the same as that of untreated cells. The fractionated irradiation did not affect the capacity of the cells to perform DNA repair synthesis. Likewise, the sensitivity to inhibition by acute radiation exposure of the ability to induce ornithine decarboxylase activity was similar in cells exposed to fractionated irradiation and in untreated cells. It is concluded that there is no apparent effect of sublethal radiation dose received in one generation on the radiation sensitivity of the succeeding generations during the log-phase of growth.

Notes: Summary The possible future trends of the radiation exposure by carbon 14 have been assessed. The individual lifetime doses and the European and global dose commitments were calculated by a specific activity model. A non-linear compartment model was developed so simulate the global cycling of carbon dioxide from the combustion of fossil fuels and of radiocarbon released from nuclear energy facilities until the year 2200. The energy scenarios considered are: (I) logistic growth functions for energy supply with fossil fuels; (II) a high, low and moderate estimate for the extension of nuclear energy (light water reactors). In addition, the influence of the retention of C-14 in the fuel reprocessing plant effluents was tested. For most of the scenarios considered the increase of the specific activity by C-14 releases is more than compensated by the C02 releases from fossil fuels. Up to 2200 individual lifetime dose commitments for 70 years were found between 0.85 and 0.45 mSv (pre-industrial value: 0.73 mSv). The anthropogenic contributions to the global collective dose commitments until the year 2100 were estimated (for the moderate scenario without retention) at 1.27 × 106 man-Sv (11%) from nuclear weapon tests, 3.5 × 105 man-Sv (3%) from nuclear power plants, and 6.5 × 105 man-Sv (5.6%) from fuel reprocessing facilities.

Notes: Summary The reciprocal interchange between the chromatids of a chromosome, termed sister chromatid exchange (SCE), is considered to be one of the most sensitive and accurate cytogenetic parameters and respond to toxic chemicals at very low doses. But the response of SCE to ionizing radiation is very poor. Human lymphocytes fail to give SCE response when irradiated at G0. Probably the primary lesions induced at G0 do not remain available long enough to find expression as SCEs. Based on this assumption a schedule was developed using caffeine to demonstrate radiation induced SCEs. Following this schedule a dose-dependent increase in the frequency of radiation induced SCEs has been observed.

Notes: Summary Interaction from several agents, i.e., a greater or smaller effects than expected from the sum of the individual effects can be of essentially two types: a) The agents could act in paralell on the same target, and a term depending on the doses of the agents involved would have to be added to the individual dose effect relationships (parergic interaction). b) The agents could act at different points in the chain of events leading to the observed effect, and the action of the second agent, the promotor, would be, at least in part, contingent on the action of the first inducer agent so that the dose effect relationships are linked in a multiplicative manner (metergic interaction). The dose effect surfaces for interaction depend on the type of dose effect relationship of the individual agents. Formulas are given for the general cases and are exemplified in graphs. Typical isobolic diagrams are also illustrated. These formulas may be adapted to experimental data by means of non-linear regression or maximum-likelihood analysis.

Notes: Summary The effect of ionizing irradiation on the physiological activity of cyclic adenosine monophosphate (cAMP) in smooth muscle preparations from frog lung was studied. cAMP, given as dibutyryl salt (dib-cAMP) inhibited the radiation induced contractions of the muscle in a manner similar to the action of theophylline. In vitro irradiation of dib-cAMP resulted in an alteration of the chemical structure of this substance, i.e., formation of monobutyryl-cAMP and further derivatives as well as a decomposition of the purine structure. There was also a loss of the relaxing activity of irradiated cAMP on the muscle tone of frog lung preparations. The physiologically measured inactivation of dib-cAMP was far more pronounced than the chemical alteration. An inhibitory effect of the reaction products is postulated.

Notes: Summary Distributions of absorbed dose in linear energy transfer (LET) and in lineal energy (y) are calculated for beams of negatively charged pions in a water phantom. The calculation is based on a comprehensive set of experimental data. The production ofδ-ray electrons by fast particles is taken into account semiempirically. The results are compared with experimentally obtained spectra of ionization yields. The equivalence of data derived from pion nucleus interaction and taken from microdosimetry is clearly revealed. The distribution of absorbed dose is given in a sequence of contributions from the various secondary particles, i.e., the socalled ‘star’ particles emitted following a nuclear capture process or the recoil nuclei from pion scatterings. This unique feature of calculated spectra will be useful for a characterization of the beam quality in view of the existing dependence of biological effects on track structure properties.

Notes: Summary Ferrokinetic perturbances in peripheral blood of mice treated with90Sr-90Y were demonstrated previously. This paper deals with the effects of90Sr-90Y treatment (2.5, 5, and 10 µCi/mouse), on the haemopoietic stem cell compartment and on the immune-status. The frequency and kinetics of haemopoietic stem cells in femoral marrow (determined as colony forming units in spleen, CFU-s) and their haemopoietic efficiency (as gauged by59Fe-and125IUdR-uptake) were estimated. The responsiveness of splenic lymphocytes of the same animals to mitogens (Con A, PHA, and LPS) were also measured. In all assays striking dose-dependent changes marked either by depressions or overshoots were observed during the first week post-incorporation. These are correlated with the pattern of deposition (primary and secondary) of the radionuclides90Sr-90Y. Towards the end of the period of observation and presumably thereafter, the dependence on dose disappeared and the values remained subnormal. An exception to this was the response of splenic lymphocytes to mitogens. Much higher reactivity was recorded up to the end. This higher reactivity is attributed to augmented cellular turnover, the newly recruited lymphocytes (in accord with their extreme radiosensitivity), being probably more reactive.

Notes: Summary The oxyhemoglobin saturation (HbO2) of single red blood cells within tumor microvessels (diameter: 3–12 µm) of DS-Carcinosarcoma was studied using a cryophotometric micromethod. In untreated control tumors (mean tissue temperature approx. 35° C) the measured values scattered over the whole saturation range from zero to 100 sat.%, the mean being 51 sat.%. Upon heating at 40° C for 30 min, the oxygenation of the tumor tissue significantly improved as compared with control conditions. After 40° C-hyperthermia a mean oxyhemoglobin saturation of 66 sat.% was obtained. In contradistinction to this, after 43° C-hyperthermia the tumor oxygenation was significantly lower and reached a mean HbO2 saturation value of 47 sat.%. A further temperature rise to 45° C caused the oxygenation to drop drastically (mean oxyhemoglobin saturation value: 24 sat.%). This is due to a severe restriction of nutritive blood flow. The changes in tumor oxygenation after hyperthermia seem to be predominantly mediated through changes in tumor blood flow, including tumor microcirculation, which showed a similar temperature dependence. Metabolic effects probably play a minor role in the oxyhemoglobin saturation distribution within tumor microvessels.

Notes: Summary Computing parameters of primary productivity models from empirical data encounters the difficulty that Liebig's law of minimum is involved. For many of the data points used to fit the model it may not be evident which factor is the respective limiting one; it may even be different from the independent variables used. The introduction of a suitable statistical data model, however, allows a Maximum Likelihood procedure to be applied which simultaneously optimizes the parameters and classifies the data. Moreover, the proposed procedure is quite insensitive to data points whose limiting factor is not contained in the actual set of independent variables. Applicability of the method is demonstrated using a set of productivity measurements compiled by H. Lieth in 1975; numerical results, of course, may be subject to change as more data become available.

Notes: Summary The recent developments in the field of membrane biology of eukaryotic cells result in revival of relevant radiobiological studies. The spatial relations and chemical nature of membrane components provide rather sensitive targets. Experimental data are presented concerning the effects of relatively low doses of X-irradiation and low concentration of tritiated water (HTO) on variou receptor function - concanavalin A, cationized ferritin, poliovirus - of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the multifold roles of radiation-induced membrane phenomena on the development and regeneration of radiation injuries. Invited plenary lecture presented at 16th Annual Meeting of the European Society for Radiation Biology, Krakow, Poland, 7–10 September 1981

Notes: Summary Measurements of the concentrations of222Rn, its short-lived decay products and of212Pb -212Bi were performed in 150 dwellings and in the open air in the Federal Republic of Germany. The concentration of222Rn was measured by electrostatic deposition of218Po. The concentrations of the short-lived decay products were measured by air sampling and alpha-spectroscopy. It was found that inside dwellings the average potential alpha-energy concentration of the short-lived daughters is about three times higher than in the open air. The total potential alpha-energy concentration indoors amounts to 2.6 · 10−3 Working Level (W. L.). Direct measurements of the equilibrium factor inside dwellings gave a mean value of 0.3. A strong dependence of the potential alpha energy concentration on the ventilation rate in dwellings has been observed. These ventilation effects exceed the effects caused by differences in the activity concentrations due to different building materials. The dose calculation results in an average dose to the whole lung due to the inhalation of short-lived radon daughters of about 0.05−0.2 mGy/a. An estimate of risk - based on the risk factors for uranium miners - shows an average lifetime risk of about 6 · 10−4 for the incidence of lung cancer caused by inhalation of radon and thoron daughters in dwellings in the Federal Republic of Germany.

Notes: Summary A sequential study of the acute effects of prenatal X-irradiation on telencephalic cell population dynamics was performed by combining a pathological evaluation with autoradiographic methods. This study confirmed that a dose of 0,95 Gy affects nearly all neuroblasts in the G1-, G2-, and M-stage lethally. Within ventricular cells staying in the S-phase at the time of X-irradiation, lethal effects are in the range between 50% and 75%. The surviving remainder of these neuroblasts is responsible for subsequent attempts for regeneration of the telencephalic roof. Two subpopulations of the surviving S-phase cells were observed: The first subpopulation which seems to be restricted to the rudiments of the ventricular zone shows a S/G2-blockade for 8–12 h after X-irradiation. Thereafter these cells start again with mitotic activity. The second subpopulation is morphologically manifested by the formation of heterotopic cell nests, i.e., so-called rosettes. These cells continue with an intense DNA-replication after the 12th h post irradiation and proceed to the mitosis stage only after about another 4–8 h, i.e., the 16th to 20th hour following X-irradiation. These findings indicate the existence of two different pools of regenerative cells within the telencephalic roof, giving rise to either orthotopic or heterotopic growth processes after irradiation injury.

Notes: Summary Microwave absorption at 1.29 GHz in an upright sitting rhesus model was studied using a gradient-layer, envelope calorimeter. Various body members of the model such as the arms, legs, head and neck, etc. were individually studied in separate experiments. Results of these experiments showed a major fraction of the overall microwave absorption to be occurring in the extremities rather than in the central trunk of the model. These results have corroborated previous dosimetric information obtained with a nonperturbing temperature probe. The overall average specific absorption rate was about twice that predicted from available theoretical methods, and a multibody interaction resonance in the lower legs, and to some extent the arms, is believed to have produced the enhanced absorption. Based on these results it is predicted that a relatively strong leg absorption would occur in a sitting human for similar irradiation conditions at frequencies between 500 and 700 MHz.

Notes: Summary The body content of certain radionuclides and the consequences of accidental incorporation may be reduced by treatment with chelating agents. Such agents have been widely studied and have proved to be useful in man. Chelation therapy may also be advantageous in certain cases of heavy metal poisoning. There is still a need to develop new, more efficient and less toxic agents and better therapeutic schedules for using the existing agents. So far as possible the testing of potential new compounds should be carried out using standardized methods.

Notes: Summary An integrated approach to study the effects of environmental factors on plants is described. The central theme of the system is the use of CO2 labelled with11C supplied continuously to the plant and following the emitted radiation in vivo in the leaf, the phloem and the various sinks. The system consists of six components and with minor changes can be used for other tracers such as13N for nitrogen fixation studies. Because of the short half life of the isotope, several experiments can be carried out on the same plant under the same environmental conditions without disturbing the plant. A host of ecologically, agriculturally and genetically important questions can be answered using this technique.

Notes: Summary The microvasculature of the neonatal rat brain and its radiation-induced petechial hemorrhages were used as an in vivo model for studying the effect of negative pions on healthy normal tissue. By means of dose response curves (range: 2–6 gray) the RBE of peak pions with respect to 220 kVp X-rays was calculated. Whereas earlier studies involved irradiations with single beam pions (πE3) of low dose rate (0.06–0.11 Gy per min) the present work was performed using pions of a multiport applicator (Piotron) of higher dose rate (1 Gy per min). The results obtained by Piotron pions agreed well with those obtained byπE3 pions resulting in a RBE of 1.1. The difference between pion and X-rays, however, was statistically not significant. 0-(beta-hydroxyethyl)-rutosides known for their protective effect on radiation damage induced by either X-rays or electrons were used for evaluating any radioprotective effect on pion-induced damage of the microvasculature. They were applied subcutaneously in doses of 450 mg/kg body weight 30 min prior to irradiation. It could be demonstrated that the rutosides decreased the pion-induced radiation response significantly by a factor of 1.3.

Notes: Summary A technique for determining the double strand break (dsb) yield in irradiated iso-disperse DNA using the molecular length profile of the damaged DNA is described. The technique employs visualisation of the irradiated DNA fragments on the electron microscope followed by length measurement of a randomly selected sample. The range of damage index measurable (0.01–1 dsb/106 Dalton) is substantially greater than that accessible by techniques involving centrifugation. Moreover the use of the whole profile of molecular lengths in the irradiated sample allows errors in the determination to be assessed. Results of experiments with T7 bacteriophage DNA irradiated in dilute aqueous solution indicate that the observed molecular length profiles are in good agreement with those generated theoretically assuming random breakage. The techniques for fitting observed profiles by the method of maximum likelihood to those generated theoretically are described in detail in an appendix. There is no evidence of bias caused by preferential losses in any part of the length profile.

Notes: Summary In a previous publication it has been shown that the radiation induced physiological inactivation of dibutyryl-cAMP was far more pronounced than the chemical modification (Schachinger et al. 1981). In this paper it will be shown, that irradiation of dib-cAMP in solution resulted in the formation of monobutyryl cAMP and other not yet completely identified hydroxylated derivatives as well as a decomposition of the purine structure. Moreover, irradiated dib-cAMP inhibited the physiological activity of not irradiated dib-cAMP on the smooth muscle. From the data an effectiveK m -value for dib-cAMP of 2.4 × 10−5 M was determined and an effectiveK I -value of 1.3 × 10−6 M was found for the irradiation products, i.e., a tenfold affinity of the latter compared to unirradiated dib-cAMP. The results are discussed with respect to a better understanding of dose-response curves for chemical and physiological inactivation.

Notes: Summary In order to ascertain the main target of the photodynamic effect with the sensitizer thiopyronine (TP) and its interference with cellular DNA, the uptake of TP into the yeastSaccharomyces cerevisiae and the distribution of the dye within the cells were studied. After fractionation of the cellular components, about 1% of the TP was found to be bound to the nucleus in anaerobically grown yeast cells; in aerobically grown cells, about 7% could be detected at the mitochondria. After careful isolation of the DNA from the organelles, only 0.024% of the dye once taken up by the cells was detectable at nuclear DNA, whereas 0.652% was bound to mitochondrial DNA. A calculation of the number of TP-molecules bound per nucleotides revealed a ration of one molecule TP per about 6,000 nucleotides of nuclear DNA and one molecule TP per 53 nucleotides of mitochondrial DNA. In vitro, the maximal binding capacity was estimated to be about one molecule TP per nucleotide. The induction of single strand breaks in the DNA after photodynamic treatment in vivo and in vitro was investigated by comparing the sedimentation of nDNA and mtDNA through alkaline sucrose-gradients. No differences in the sedimentation profiles of nDNA after photodynamic treatment of the cells in vivo as compared to the untreated control could be observed. In contrast, the sedimentation coefficient of mtDNA was significally decreased after photodynamic treatment, indicating the induction of single strand breaks in vivo only in mtDNA and not in nDNA.

Notes: Summary The redox potential as a basic aquatic system component generally receives little attention. The reason for this is the widely spread assumption that the platinum electrode reacts basically to an oxygen dominated redox system. Consequently no satisfying interpretation of measurements would be possible. This erroneous assumption led to the opinion that the redox potential could only serve as a relative measure. Intensive studies in 22 water bodies, predominantly in lakes from the younger moraine area of Schleswig-Holstein, Northern Germany, yielded definite clues to six different redox systems. Depending on the physico-chemical conditions one of these becomes the dominant system determining the electric potential. The “redox equations” seem to apply to all alkaline dominated water bodies such as calcium dominated freshwater lakes, brackish water bodies, sea water and sometimes even hydromorphic soils, sediments and sewage sludge. The equations do not apply to humus rich water bodies such as water from peat bogs and black water streams. Based on these findings the present paper deals with ecosystem relevant results obtainable from redox measurements: pH-measurements revealed a pronounced relationship between pH-value and the intensity of autotrophic production, the redox potential measured in aerobic waters mainly reflected the alternations of NO 3 − and NO 2 − , i.e., during the summer the assimilation of NO 3 − by algae and excretion of NH 4 + , NO 2 − , and NO 3 − by ammonifying and nitrifying bacteria. During winter a slow oxidation of reduced N-compounds by nitrifying heterotrophs was assumed, stagnant conditions in the deep water layers during summer led to a more or less rapid lowering of redox potential depending on the trophic level of the lake. Changes from one redox system to the next became observable. The investigations revealed an intimate relationship between the potential measured and the type of metabolism favored.

Notes: Summary Mammalian cell mutants with defective repair of UV-induced DNA damage can be identified by the lack of unscheduled incorporation of radioactive thymidine into DNA after UV irradiation. With a specially designed windowlessMultiWireProportionalChamber (MWPC), colonies with absent or low incorporation of3H-thymidine can be precisely located within a population of normally labelled colonies. The main advantages of MWPC analysis over other more conventional methods for radioactive measurements are: (i), cells are not harmed by the analysis, so that previous replica plating of colonies becomes unnecessary; (ii), measurements are quantitative, hence discrimination between colonies is not subjective; (iii), location of unlabelled, non-repairing colonies is rapid and can be automatized. The method therefore appears suitable for the isolation of mammalian cell mutants with a block in DNA repair.

Notes: Summary Mouse embryos on day 8 of gestation were irradiated with negative pions (12.5–100 rad) or 200 kV X-rays (12.5–150 rad). Misonidazole (MISO), a hypoxic cell radiosensitizer, was applied 30 min before exposure. On day 13 the fetuses were examined for lethality, growth retardation and malformation. No significant embryolethal effects were observed after irradiation alone in the dose range of 12.5–100 rad (X-rays or pions). However, MISO alone and in combination with radiation led to high rates of lethality. The frequency of growth retardation was significantly increased at 100 rad and in combined treatments at low radiation doses. MISO and irradiation with 50 rad and more induced complex damages consisting of multiple and severe malformations and growth retardation. The relative biological effectiveness (RBE) for teratogenic effects was 1.6. In conclusion, the combined application of MISO and radiation of different LET revealed a strong enhancing action compared to single treatments. The extent of enhancement depends on both radiation quality and dose.

Notes: Summary Cultured mouse L5178Y cells were irradiated at room temperature with various doses of X-rays, and the rate of3H-thymidine incorporation was followed for 2 1/2 h after exposure. The rate of3H-thymidine incorporation is affected by two factors; inhibition and resumption of replicon initiation, and chain elongation. A simple method has been developed for estimating the amount of thymidine incorporation which is accounted for by DNA chain elongation after irradiation. This then allows an analysis of the inhibition and resumption of replicon initiation caused by X-rays. The method is based on knowledge of the rate of DNA chain elongation and of the distribution of replicon sizes which are determined by fiber autoradiography. The duration of the inhibition of replicon initiation and the initial slope of the curve showing recovery of initiation were obtained by subtracting the DNA synthesis due to chain elongation from the overall rate of3H-thymidine incorporation. The interval of depressed DNA synthesis increased with increasing dose of X-rays but only gradually at doses higher than 500 rad. The interval did not exceed 60 min even after 5,000 rad. The initial shope of the curve showing recovery of initiation decreased in a dose dependent manner but very slowly at doses higher than 1,000 rad of X-rays. It appears likely that this initial slope correlates with the relative number of replicons initiating synthesis at the beginning of the recovery period.

Notes: Summary The method of iteratively reweighted least squares for the regression analysis of Poisson distributed chromosome aberration data is reviewed in the context of other fit procedures used in the cytogenetic literature. As an application of the resulting regression curves methods for calculating confidence intervals on dose from aberration yield are described and compared, and, for the linear quadratic modelλ =β 0 +β 1 x +β 2 x 2 a confidence interval for the ratioβ 1/β 2 is given. Emphasis is placed on the rationale, interpretation and the limitations of various methods from a statistical point of view.

Notes: Summary Experimental results obtained with the neutral sucrose gradient sedimentation techniques of analysing mammalian DNA after irradiation in vivo (Chinese hamster cells V79) are evaluated theoretically in order to verify and extend a model by Ormerod and Lehmann that describes the gradual release of free DNA from the DNA-membrane complex. The model is based on the idea of chromatin organization in the form of membrane attached superstructure units (MASSUs) defined by consecutive attachment points in intervals ofM 0 (DNA molecular weight of a MASSU). DNA sedimentation after cell lysis with sarkosyl as detergent allows good separation of the released free DNA from that remaining in the complex. The dose-dependence of both the percentage of DNA released and pertinent molecular weight parameters as measured with X-rays and derived from the model confirms it and yields the MASSU sizeM 0 = 2.4 × 109 g/mol. Furthermore, the model is evaluated with respect to high-LET radiations by a mathematical theory based strictly on microdosimetry. This approach, which could be of general interest as a contribution to theoretical microdosimetry, reduces the measurable quantities explicitly to the single event distribution of lineal energy for the gross volume,V, occupied by a MASSU in the interphase nucleus. Experimental results obtained withα-particles agree with this extended version of the model, yielding 0.2 – 0.3 µm for the diameter ofV. In summary, the following conclusions are drawn: The entire chromatin, at least the greater part of it, must be organized in regular superstructure units with no detectable variance of their lengthsM 0, which is suggested to be a general principle whose functional implications remain to be elucidated.

Notes: Summary In experiments on glucose-6-phosphatase and tyrosine amino-transferase it was shown that radiation induces changes in enzymic differentiation in perinatal rat liver. A study was made of the probable reasons for the observed changes. It was shown that the macromolecular system of the protein enzyme synthesis was not damaged by the radiation doses used. The observed decrease in glucose-6-phosphatase activity during late embryogenesis, after pre-irradiation at early organogenesis, is eliminated by administration of exogenous thyroxine. A radiation-induced rise in the tyrosine aminotransferase activity during the perinatal period correlated with the cyclic AMP system status. It is proposed that modification of enzymic differentiation after irradiation results from the change in the amount of inductors.

Notes: Summary The effect of single or fractionated doses of stopping pions or 200 kV X-rays on the mouse jejunal crypt cells was used to determine in vivo RBE values. For single fraction, the pion/X-ray RBE was 1.27 and it increased to about 1.31 when two fractions were applied at 3 or 24 h interval. When four fractions were given at 3 h intervals, the RBE was 1.46. This is because the fraction of “dose repaired” was always higher for X-rays than for pions and this difference was enhanced when more dose fractions were used. The data presented is, in general, consistent with the biological effects of pions reported for other in vivo end points.

Notes: Summary Using the Chinese hamster cell line B14 FAF28, several specific properties of the contact effect (CE) of radiation action in spheroids were investigated. CE was found to “protect” the spheroid cells against several types of radiation-induced cytogenetic misfunctions such as blockage in S and G2+M-phase, mutagenesis, and chromosome damage. However, repair of DNA strand-breaks was the same in monolayers and spheroids. Furthermore, CE is a property of the single cell and does not depend on the proliferative status (cycling or non-cycling) of the cells. We conclude that CE is the result of a physiological modification of the cells occurring during growth in the three-dimensional spheroid matrix and requiring metabolic cooperation and cyclic AMP for its induction.

Notes: Summary A combined treatment of pregnant mice on day 12 of gestation with both azacytidine and X-irradiation in low doses induces sequence-dependent histological effects. These effects, in turn, induce different symptomatic signs if evaluated either prenatally or neonatally. In the azacytidine treatment/X-irradiation sequence the malformations of the fetal forebrain are predominant. Consequently, these dams show a high incidence in the stillbirth rate. Conversely, the X-irradiation/azacytidine treatment schedule leads only to a mild brain hypoplasia, and does not cause an increased stillbirth rate. In these offspring, however, a severe impairment of small bowel epithelial proliferation capacity was found. This is linked to an outstanding neonatal mortality within 48 h after birth. The pathogenesis of these sequence-dependent effects can be attributed to a selective vulnerability of cells in different stages of the generation cycle. This comprises a high degree of cytolethality affecting the S/G2-stage cells in azacytidine/X-irradiation treatment and the G1/S-stage cells in the reverse combinations (Schmahl 1979). The present observations show the validity of a teratological assay in providing a detailed analysis of the cell kinetic responses after combined noxious influences.

Notes: Summary High energyα-particles (∼ 16 MeV) and 254 nm ultraviolet light produced dose dependent linear increase of lipid hydroperoxides in the dried thin film state. For both types of radiation, an inverse dose-rate effect, i.e., a protracted radiation dose was more effective than a shorter, more intense one of larger size, was observed. Ultraviolet light (254 nm) produced higher yields of hydroperoxides in the aqueous liposomal suspension of lipid than in its dried thin film state.

Notes: Summary The RBE of Cf-252 neutron irradiation was determined for hemopoietic tissue using spleen CFU-S. Radiosensitivity was compared to acute Cobalt-60 radiation and low dose rate Cesium-137 under identical irradiation conditions. The RBE for the neutron component of the Cf-252 radiation was 2.1. No dose rate effect was observed for hemopoietic CFU-S to acute doses or low dose rate photon irradiation.