Skip to main content
Log in

Subclinical effects of groundwater contaminants I: Alteration of and cellular immunity by benzene in CD-1 mice

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Benzene is a known contaminant found in trace amounts in ground water. It has long been associated with myelotoxicity and associated immunologic effects. The present study concerned the immunotoxic potential of benzene following four weeks of continuous oral administration via drinking water at concentrations of 0, 31, 166 and 790 mg/L. Benzene-treated water produced a dose-related decrease in spleen weight and increase in kidney weight; both were significantly different at the highest level. Benzene exposure caused a significant dose-response reduction of peripheral blood leukocytes, lymphocytes, erythrocytes and resulted in a severe macrocytic anemia. Splenic lymphocyte proliferation to both B cell and T cell mitogens [lipopolysaccharide (LPS), pokeweed mitogen (PWM), concanavalin A (Con A) and phytohemagglutinin (PHA)] was followed by a dose-related biphasic responsiveness, enhanced at the lowest dose (31 mg/L) and depressed in the higher dosage groups (166 and 790 mg/L). Cell-mediated immunity as measured by mixed-lymphocyte culture (MLC) response to allogeneic cells and cytotoxic T lymphocyte (CTL) activity to YAC-1 tumor ceils exhibited similar biphasic phenomenon. Antibody production as assessed by enumeration of the sheep red blood cell (SRBC)-specific plaque-forming cells (PFC) indicated a significant suppression of PFC in animals exposed to 166 and 790 mg/L benzene. A decrease in the α-SRBC-antibody titer corresponded to the numbers of PFC. The findings suggest that oral ingestion of benzene, at the concentrations utilized, produced a biologically significant immunotoxic effect on both the humoral and cellular immune responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aoyama K (1986) Effects of benzene inhalation on lymphocyte subpopulations and immune response in mice. Toxicol Appl Pharmacol 85:92–101

    PubMed  Google Scholar 

  • Aranyi C, O'Shea WJ, Graham JA, Miller JF (1986) The effects of inhalation of organic chemical air contaminants on murine lung host defenses. Fundam Appl Toxicol 6:713–720

    PubMed  Google Scholar 

  • Baarson KA, Snyder CA, Albert RE (1984) Repeated exposure of C57B1 mice to inhaled benzene at 10 ppm markedly depressed erythropoietic colony. Toxicol Lett 20:337–342

    PubMed  Google Scholar 

  • Bick H, Holsapple MP, White KL (1985) Assessment of the effects of chemicals on the immune system. In: Li AP (ed) New Approaches in Toxicity Testing and Their Application in Human Risk Assessment. Raven Press, New York, pp 165–177

    Google Scholar 

  • Bolcsak LE, Nerland DE (1983) Inhibition of erythropoiesis by benzene metabolites. Toxicol Appl Pharmacol 69:363–368

    PubMed  Google Scholar 

  • Brief RS, Lynch J, Bereath T, Scala RA (1980) Benzene in the workplace. Am Ind Hyg Assoc J 43:616–623

    Google Scholar 

  • Cunningham AJ, Szenberg A (1968) Further improvements in the plaque technique for detecting single antibody producing cells. Immunology 14:599–601

    PubMed  Google Scholar 

  • Dean BJ (1985) Recent findings on the genetic toxicology of benzene, toluene, xylenes, and phenols. Mutation Res 154:153–181

    PubMed  Google Scholar 

  • Dean JH, Luster MI, Boorman GA, and Lauer LD (1982) Procedures available to examine the immunotoxicity of chemicals and drugs. Pharmacol Rev 34:137–151

    PubMed  Google Scholar 

  • Dempster AM, Evans HL, Snyder CA (1984) The temporal relationship between behavioral and hematological effects of inhaled benzene. Toxicol Appl Pharmacol 76:195–203

    PubMed  Google Scholar 

  • Dinarello CA, Mier JW (1986) Interleukins. Ann Rev Med 37:173–178

    PubMed  Google Scholar 

  • Dowdy S, Wearden S (1983) Statistics for research. John Wiley & Sons, New York

    Google Scholar 

  • Faith RE, Luster MI, Vos JG (1980) Effects on immunocompetence by chemicals of environmental concern. Ann Rev Biochem Toxicol 2:173–211

    Google Scholar 

  • Fishbein I (1984) An overview of environmental and toxicological aspects of aromatic hydrocarbons. 1. Benzene. Sci Total Environ 40:189–218

    PubMed  Google Scholar 

  • Gaido K, Wierda D (1984)In vitro effects of benzene metabolites on mouse bone marrow stomal cells. Toxicol Appl Pharmacol 76:45–55

    PubMed  Google Scholar 

  • Garnett HM, Cronkite EP, Drew RT (1983) Effect ofin vivo exposure to benzene on the characteristics of bone marrow adherent cells. Leukemia Res 7:803–810

    Google Scholar 

  • Grabstein K (1980) Cell-mediated cytolytic responses. In: Mishell BB, Shiigi SM (eds) Selected Methods in Cellular Immunology. WH Freeman, San Francisco, pp 124–137

    Google Scholar 

  • Green JD, Snyder CA, LoBue J, Goldstein BD, Albert RE (1981) Acute and chronic dose/response effects of benzene inhalation on the peripheral blood, bone marrow, and spleen cells of CD-1 male mice. Toxicol Appl Pharmacol 59:204–214

    PubMed  Google Scholar 

  • Greenlee WF, Sun JD, Bus JS (1981) A proposed mechanism of benzene toxicity. Formation of reactive intermediates from polyphenol metabolites. Toxicol Appl Pharmacol. 59:187–195

    PubMed  Google Scholar 

  • Haley, T (1977) Evaluation of the health effects of benzene inhalation. Clin Toxicol 11:531–548

    PubMed  Google Scholar 

  • Hanahan DJ, Ekholm JE (1974) The preparation of red cell ghosts (membranes). Methods Enzymol XXXI: 168–172

    Google Scholar 

  • Harigaya K, Miller ME, Cronkite EP, Driw RT (1981) The detection ofin vivo hematoxicity of benzene byin vitro liquid bone marrow cultures. Toxicol Appl Pharmacol 60:346–353

    PubMed  Google Scholar 

  • Irons RD (1985) Quinones as toxic metabolites of benzene. J Toxicol Environ Hlth 16:673–678

    Google Scholar 

  • Jerne NK, Nordin AA (1963) Plaque formation in agar by single antibody-producing cells. Science 140:405–407

    Google Scholar 

  • Kaplan HS (1967) On the natural history of the murine leukemias. Cancer Res 27:1325–1340

    PubMed  Google Scholar 

  • Longacre SL, Kocsis JJ, Snyder R (1981) Influence of strain differences in mice on the metabolism and toxicity of benzeae. Toxicol Appl Pharmacol 60:398–409

    PubMed  Google Scholar 

  • Moszczynsky P, Lisiewicz J (1984) Occupational exposure to benzene, toluene and xylene and the T lymphocyte functions. Haematologia 17:449–453

    PubMed  Google Scholar 

  • Pandya KP, Shanker R, Gupta A, Khan WA, Ray PK (1986) Modulation of benzene toxicity by an interferon inducer (GMFA). Toxicology 39:291–305

    PubMed  Google Scholar 

  • Pfeifer RW, Irons RD (1982) Effect of benzene metabolites on phytohemagglutinin-stimulated lymphopoiesis in rat bone marrow. J Reticuloendothel Soc 31:155–170

    PubMed  Google Scholar 

  • Post GB, Snyder R, Kalf GF (1985) Inhibition of RNA synthesis and interleukin-2 production in lymphocytesin vitro by benzene and its metabolites, hydroquinone, andp-benzoquinone. Toxicol Lett 29:161–168

    PubMed  Google Scholar 

  • Rosenthal GJ, Snyder CA (1985) Modulation of the immune response toListeria monocytogenes by benzene inhalation. Toxicol Appl Pharmacol 80:502–510

    PubMed  Google Scholar 

  • Rozen MG, Snyder CA (1985) Protracted exposure of C57B1/6 mice to 300 ppm benzene depresses B- and T-lymphocyte numbers and mitogen responses. Evidence for thymic and bone marrow proliferation in response to the exposures. Toxicology 37:13–26

    PubMed  Google Scholar 

  • Rozen MG, Snyder CA, Albert RE (1984) Depression in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene. Toxicol Lett 20:343–349

    PubMed  Google Scholar 

  • Sawahata T, Rickert DE, Greenlees WE (1985) Metabolism of benzene and its metabolites in bone marrow. In: Irons RD (ed) Toxicology of the Blood and Bone Marrow. Raven Press, New York, pp 141–148

    Google Scholar 

  • Schwartz CS, Snyder R, Kalf GF (1985) The inhibition of mitochondrial DNA replicationin vitro by the metabolites of benzene, hydroquinone andp-benzoquinone. Chem Biol Interac 53:327–350

    Google Scholar 

  • Sharma RP, Gehring PJ (1979) Immunologic effects of vinyl chloride in mice. Ann NY Acad Sci 320:551–563

    PubMed  Google Scholar 

  • Snyder CA, Goldstein BD, Sellakumar A, Bromberg I, Laskin S, Albert RE (1982) Toxicity of chronic benzene inhalation: CD-1 mice exposed to 300 ppm. Bull Environ Contam Toxicol 29:385–391

    PubMed  Google Scholar 

  • — (1980) The inhalation toxicology of benzene: Incidence of hematopoietic neoplasms and hematotoxicity in ARK/J and C57BL/6J mice. Toxicol Appl Pharmacol 54:323–331

    PubMed  Google Scholar 

  • US Environmental Protection Agency (1980) Ambient Water Quality Criteria for Benzene. (EPA 440/5-80-018). Washington, DC

  • - (1982) Test Methods for Evaluating Solid Waste. Physical/Chemical Methods. 2nd Edition. Office of Solid Waste and Emergency Response. SW-846. Washington, DC

  • Voller A, Bidwell DE, Bartlett A (1979) The enzyme linked immunosorbent assay (ELISA). A guide with abstracts of microplate applications. Dynatech Laboratories, Alexandria, VA

    Google Scholar 

  • Walker PP, Walker JK, Evans HH, Blumer JL (1985) Relationship between the oxidation potential of benzene metabolites and their inhibitory effect of DNA synthesis on L5178YS cells. Molec Pharmacol 28:560–566

    Google Scholar 

  • Wierda D, Irons RD (1982) Hydroquinone and catechol reduce the frequency of progenitor B-lymphocytes in mouse spleen and bone marrow. Immunopharmacology 4:41–54

    PubMed  Google Scholar 

  • Wierda D, Irons RD, Greenlee WF (1981) Immunotoxicity in C57BL/6 mice exposed to benzene and Aroclor 1254®. Toxicol Appl Pharmacol 60:410–417

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hsieh, G.C., Sharma, R.P. & Parker, R.D.R. Subclinical effects of groundwater contaminants I: Alteration of and cellular immunity by benzene in CD-1 mice. Arch. Environ. Contam. Toxicol. 17, 151–158 (1988). https://doi.org/10.1007/BF01056019

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01056019

Keywords

Navigation