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  • 1
    Electronic Resource
    Electronic Resource
    Development of antibody-based fiber-optic sensors for detection of a benzo[a]pyrene metabolite (1988)
    s.l. : American Chemical Society
    Analytical chemistry 60 (1988), S. 1901-1908 
    Details
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ac00169a012
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  • 2
    Electronic Resource
    Electronic Resource
    Variability in PAH-DNA Adduct Measurements in Peripheral Mononuclear Cells: Implications for Quantitative Cancer Risk Assessment (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 17 (1997), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Biomarkers such as DNA adducts have significant potential to improve quantitative risk assessment by characterizing individual differences in metabolism of genotoxins and DNA repair and accounting for some of the factors that could affect interindividual variation in cancer risk. Inherent uncertainty in laboratory measurements and within-person variability of DNA adduct levels over time are putatively unrelated to cancer risk and should be subtracted from observed variation to better estimate interindividual variability of response to carcinogen exposure. A total of 41 volunteers, both smokers and nonsmokers, were asked to provide a peripheral blood sample every 3 weeks for several months in order to specifically assess intraindividual variability of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels. The intraindividual variance in PAH-DNA adduct levels, together with measurement uncertainty (laboratory variability and unaccounted for differences in exposure), constituted roughly 30% of the overall variance. An estimated 70% of the total variance was contributed by interindividual variability and is probably representative of the true biologic variability of response to carcinogenic exposure in lymphocytes. The estimated interindividual variability in DNA damage after subtracting intraindividual variability and measurement uncertainty was 24-fold. Inter-individual variance was higher (52-fold) in persons who constitutively lack the Glutathione S-Transferase M1 (GSTM1) gene which is important in the detoxification pathway of PAH. Risk assessment models that do not consider the variability of susceptibility to DNA damage following carcinogen exposure may underestimate risks to the general population, especially for those people who are most vulnerable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1997.tb00905.x
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  • 3
    Electronic Resource
    Electronic Resource
    Interaction between poly(L-lysine58, L-phenylalanine42) and deoxyribonucleic acids (1975)
    s.l. : American Chemical Society
    Biochemistry 14 (1975), S. 3604-3611 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00687a014
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  • 4
    Electronic Resource
    Electronic Resource
    Molecular and genetic damage in humans from environmental pollution in Poland (1992)
    [s.l.] : Nature Publishing Group
    Nature 360 (1992), S. 256-258 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The environmentally exposed population is from the town of Gliwice in the Province of Katowice, Silesia, which is one of the most heavily polluted areas in the world and is characterized by high cancer mortality and high infant mortality1. The average annual atmospheric concentration of ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/360256a0
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  • 5
    Electronic Resource
    Electronic Resource
    Monitoring human exposure to carcinogens by DNA adduct measurement (1988)
    Springer
    Cell biology and toxicology 4 (1988), S. 511-516 
    Details
    ISSN: 1573-6822
    Keywords: adducts ; aminopyrene, benzo[a]pyrene ; exposure ; 8-methoxypsoralen ; monoclonal antibodies ; UVA irradiation ; vinyl chloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Sensitive immunologic techniques are now available for the detection and quantitation of carcinogen-DNA adducts. We have developed a number of specific monoclonal antibodies which recognize DNA modified by particular carcinogens, including benzo[a]-py-rene, aminopyrene, 8-methoxypsoralen plus UVA light and vinyl chloride. These antibodies can be used in competitive enzyme-linked immunosorbent assays to quantitate adducts in DNA isolated from biological samples. Samples from treated animals as well as from humans with occupational or environmental exposure to carcinogens have been studied. In addition, antibodies can be used in indirect immunohistochemical studies to localize adduct formation in various tissues or cell types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00117779
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  • 6
    Electronic Resource
    Electronic Resource
    Interaction between poly(L-lysine48, L-histidine52) and DNA (1977)
    New York : Wiley-Blackwell
    Biopolymers 16 (1977), S. 1879-1894 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Poly(Lys48, His52), a random copolypeptide of L-lysine (48%) and L-histidine (52%), was used as a model protein for investigating the effects of protonation on the imidazole group of histidines on protein binding to DNA. The complexes formed between poly(Lys48, His52) and DNA were examined using absorbance, circular dichroism (CD), and thermal denaturation. Although increasing pH reduces the charges on histidine side chains in the model protein, the protein still binds the DNA with approximately one positive charge per negative charge in protein-bound regions. Nevertheless, CD and melting properties of poly(Lys48, His52)-DNA complexes still depend upon the solution pH which determines the protonation state of imidazole group of histidine side chains. At pH 7.0, the complexes show two characteristic melting bands with a tm (46-51°C) for free base pairs and a t′m (94°C) for protein-bound base pairs. The t′m of the complexes is reduced to 90°C at pH 9.2, although at this pH there is still one lysine per phosphate in protein-bound regions. Presumably, the presence of deprotonated histidine residues destabilizes the native structure of protein-bound DNA. The binding of this model protein to DNA causes a red shift of the crossover point and both a red shift and a reduction of the positive CD band of DNA near 275 nm. This phenomenon is similar to that caused by polylysine binding. These effects, however, are greatly diminished when histidine side chains in the model protein are deprotonated. The structure of already formed poly(Lys48, His52)·DNA complexes can be perturbed by changing the solution pH. However, the results suggest a readjustment of the complex to accommodate charge interactions rather than a full dissociation of the complex followed by reassociation between the model protein and DNA.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.1977.360160905
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  • 7
    Electronic Resource
    Electronic Resource
    Studies on poly(L-lysine50, L-tyrosine50)-DNA interaction (1974)
    New York : Wiley-Blackwell
    Biopolymers 13 (1974), S. 1909-1926 
    Details
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Interaction between poly(Lys50, Tyr50) and DNA has been studied by absorption, circular dichroism (CD), and fluorescence spectroscopy and thermal denaturation in 0.001M Tris, pH 6.8. The binding of this copolypeptide to DNA results in an absorbance enhancement and fluorescence quenching on tyrosine. There is also an increase in the tyrosine CD at 230 nm. The CD of DNA above 250 nm is slightly shifted to the longer wavelength which is qualitatively similar to, but quantitatively much smaller than, that induced by polylysine binding. At physiological pH the poly(Lys50, Tyr50)-DNA complex is soluble until there is one lysine and one tyrosine per nucleotide in the complex. The same ratio of amino acid residues to nucleotide has also been observed in copolypeptide-bound regions of the complex. The addition of more poly(Lys50, Tyr50) to DNA yields a constant melting temperature, Tm′, for bound base pairs at 90°C which is close to that of polylysine-bound DNA under the same condition. The melting temperature, Tm, of free base pairs at about 60°C on the other hand, is increased by 10°C as more copolypeptide is bound to DNA. As the temperature is raised, both absorption and CD spectra of the complexes with high coverage are changed, suggesting structural alteration, perhaps deprotonation, on bound tyrosine. The results in this report also suggest that intercalation of tyrosine in DNA is unlikely to be the mode of binding.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/bip.1974.360130919
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  • 8
    Electronic Resource
    Electronic Resource
    Molecular epidemiology of lung cancer and the modulation of markers of chronic carcinogen exposure by chemopreventive agents (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 119-128 
    Details
    ISSN: 0730-2312
    Keywords: molecular epidemiology ; biomarkers ; lung cancer ; chemoprevention ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Chronic inhalation exposure to environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs), cigarette smoke, 4-aminobiphenyl (4-ABP), ethylene oxide, and styrene is associated with elevations in biomarkers such as DNA adducts, protein adducts, sister chromatid exchanges (SCEs), chromosomal aberrations, gene mutation, and/or oncogene activation. These biomarkers indicate an increased cancer risk for the exposed population, although quantitative estimates cannot be made with certainty. There is convincing epidemiological evidence that the antioxidant and free radical-scavenging vitamins C and E and β-carotene (β-C) protect against cancer of the lung and other epithelial tissues, with somewhat weaker evidence for retinol. Experimental studies demonstrate that these micronutrients are capable of blocking or reducing tumor formation caused by diverse carcinogens. A variety of mechanisms appear to be involved, including suppression of carcinogen activation, enhancement of carcinogen detoxification, induction of cellular differentiation, inhibition of mutagenesis, enhancement of immunologic function, and/or reduction of the formation of carcinogen-DNA adducts, SCEs, micronuclei, and other markers of genotoxic damage. Therefore, we have recently investigated the possible modifying effect of serum vitamins C and E, β-C, and retinol on a number of such biomarkers in a case-control study of lung cancer, and in a cross-sectional study of heavy smokers. Preliminary results indicate an inhibitory effect of certain vitamins on DNA adduct formation. A significant number of human intervention trials are ongoing involving these vitamins. It appears that biomarkers can provide useful intermediate endpoints for assessment of both the mechanisms and the efficacy of chemopreventive agents.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531017
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  • 9
    Electronic Resource
    Electronic Resource
    Alternative conformations of DNA modified by N-2-acetylaminofluorene (1981)
    New York, NY : Wiley-Blackwell
    Journal of Supramolecular Structure and Cellular Biochemistry 17 (1981), S. 231-244 
    Details
    ISSN: 0275-3723
    Keywords: acelylammofluorene ; Z-DNA ; base displacement model ; DNA conformation ; circular dichroism (CD) ; NMR ; nuclease S1 digestion ; Chemistry ; Molecular Cell Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Modification of DNA by the carcinogen N-acetoxy-N-2-acetylaminofluorene gives two adducts, a major one at the C-8 position of guanine and a minor one at the N-2 position with differing conformations. Binding at the C-8 position results in a large distortion of the DNA helix referred to as the “base displacement model” with the carcinogen inserted into the DNA helix and the guanosine displaced to the outside. The result is increased susceptibility to nuclease S, digestion due to the presence of large, single-stranded regions in the modified DNA. In contrast, the N-2 adduct results in much less distortion of the helix and is less susceptible to nuclease S1 digestion.A third and predominant adduct is formed in vivo, the deacetylated C-8 guanine adduct. The conformation of this adduct has been investigated using the dimer dApdG as a model for DNA. The attachment of aminofluorene (AF) residues introduced smaller changes in the circular dichroism (CD) spectra of dApdG than binding of acetylaminofluorene (AAF) residues. Similarly, binding of AF residues caused lower upfield shifts for the H-2 and H-8 protons of adenine than the AAF residues. These results suggest that AF residues are less stacked with neighboring bases than AAF and induce less distortion in conformation of the modified regions than AAF.An alternative conformation of AAF-modified deoxyguanosine has been suggested based on studies of poly(dG-dC)·poly(dG-dC). Modification of this copolymer with AAF to an extent of 28% showed a CD spectrum that had the characteristics of the left-handed Z conformation seen in unmodified poly-(dG-dC)·poly(dG-dC) at high ethanol or salt concentrations. Poly(dG)·poly(dC), which docs not undergo the B to Z transition at high ethanol concentrations, did not show this type of conformational change with high AAF modification. Differences in conformation were suggested by single-strand specific nuclease S1 digestion and reactivity with anticytidine antibodies. Highly modified poly(dG-dC)·poly(dG-dC) was almost completely resistant to nuclease S1 hydrolysis, while, modified DNA and poly(dG)·poly(dC) are highly susceptible to digestion. Two possible conformations for deoxyguanosine modified at the C-8 position by AAF are compared depending on whether its position is in alternating purine-pyrimidine sequences or random sequence DNA.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jsscb.380170305
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  • 10
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    Monitoring human exposure to carcinogens by DNA adduct measurement (1988)
    Springer
    Details
    Publication Date: 1988-12-01
    Print ISSN: 0742-2091
    Electronic ISSN: 1573-6822
    Topics: Biology , Medicine
    Published by Springer
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