Mechanisms of Benzene Toxicity

  • Suzanne Pirozzi Chatterjee
  • Robert Snyder
Part of the NATO ASI Series Advanced Science Institutes Series book series (NSSA, volume 202)


Benzene is a ubiquitous pollutant in the environment and in many workplaces. It is known to produce aplastic anemia, leukemia, chromosomal damage, and immunotoxicity. This discussion will consider mechanisms by which benzene produces decrements in bone marrow function, alters the production of cytokines, and impairs the hematopoietic system. Methods of evaluating bone marrow function such as cell counting techniques, colony forming units assays, cytokine assays, and the [59Fe] uptake technique will be summarized. Mechanisms involving covalent binding of reactive metabolites to protein and DNA which can explain the occurrence of aplastic anemia will be discussed. Implications for benzene induced leukemia and the relationship to chromosome damage will be examined. Current interest in interactions among benzene metabolites leading to toxic effects observed with benzene will be analyzed. Finally, areas where new research is needed will be proposed.


Bone Marrow Cell Aplastic Anemia Sister Chromatid Exchange Benzene Exposure Bone Marrow Cellularity 


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  1. 1.
    L. Selling, Benzol as a leukotoxin. Studies on degeneration regeneration of blood and hematopoietic organs, Johns Hopkins Hospital Rep. 17:83 (1916).Google Scholar
  2. 2.
    H.G. Weiskotten, S.C. Shwartz, H.S. Steinsland, The action of benzol on blood and blood forming tissues, J. Med. Res. 35:63 (1916).PubMedGoogle Scholar
  3. 3.
    H.G. Weiskotten, G.B.F. Gibbs, E.O. Boggs, and E.R. Templeton, The action of benzol. VI. Benzol vapor leucopenia (rabbit), J. Med. Res. 41:425 (1920).PubMedGoogle Scholar
  4. 4.
    V. Hough and S. Freeman, Relative toxicity of commercial benzene, toluene, and xylene, Fed. Proc. 3:20 (1944).Google Scholar
  5. 5.
    M. Wolf, V. Rowe, D. McCollister, R. Hollingsworth, F. Oyen Toxicological studies of certain alkylated benzenes and benzene, A. M. A. Arch. Ind. Health. 14:387 (1956).Google Scholar
  6. 6.
    W. Diechmann, W. MacDonald, E. Bemal, The hemopoietic tissue toxicity of benzene vapors, Toxicol. Appl. Pharmacol. 5:201 (1978).Google Scholar
  7. 7.
    C.A. Snyder, B. Goldstein, A. Sellakumar, S. Nohnan, I. Bromberg, M. Erlichman, and S. Laskin, Hematotoxicity of inhaled benzene to Sprague-Dawley rats and AKR mice at 300 ppm, J. Toxicol. Environ. Health. 4:605 (1978).Google Scholar
  8. 8.
    M. Tavassoli and J.M. Yoffey, “Bone Marrow: Structure and Function”, Alan R. Liss Inc., New York (1983).Google Scholar
  9. 9.
    L.S. Andrews, E.W. Lee, C.M. Witmer, J.J. Kocsis, and R. Snyder, Effects of toluene on metabolism, disposition, and hematopoietic toxicity of [14C]benzene, Biochem. Pharmacol. 26:293 (1977).PubMedGoogle Scholar
  10. 10.
    L. Andrews, H.A. Sasame, J.R. Gillette, [3H]Benzene metabolism in rabbit bone marrow, Life Sciences 25:567 (1979).PubMedGoogle Scholar
  11. 11.
    D.E. Rickert, T.S. Baker, J.S. Bus, C.S. Barrow, and R.D. Irons, Benzene disposition in the rat after exposure by inhalation, Toxicol. Appl. Pharmacol. 49:417 (1979).PubMedGoogle Scholar
  12. 12.
    D.R. Boggs, Hemostatic regulatory mechanisms of hematopoiesis, Ann. Rev. Phvsiol. 28:39 (1966).Google Scholar
  13. 13.
    A.P. Korn, R.M. Hinckelman, F.P. Ottensmeyer, and J.E. Till, Investigations of stochastic model of hemopoiesis, Exp. Hematol. 1:362 (1973).PubMedGoogle Scholar
  14. 14.
    M. Ogawa, P.N. Porter, T. Nakahata, Renewal and commitment to differentiation of hematopoietic stem cells (An Interpretive Review), Blood 61:823 (1983).PubMedGoogle Scholar
  15. 15.
    T. Nakahata, A.J. Gross, M. Ogawa, A stochastic model of self-renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture, J. Cell. Phvsiol. 113:455 (1982).Google Scholar
  16. 16.
    W.J. Williams, E. Beutler, A.J. Erslev, and R.W. Rundles, “Hematology”, 2nd ed., McGraw-Hill Book Company, New York 1977.Google Scholar
  17. 17.
    M.A. Lichtman, The ultrastructure of the hematopoietic environment of the marrow: a review, Exp. Hematol. 9:391 (1981).PubMedGoogle Scholar
  18. 18.
    J.J. Trentin, Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironment (HIM), Am. J. Pathol. 65:621 (1971).PubMedGoogle Scholar
  19. 19.
    M. Tavassoli, Studies on hemopoietic microenvironment, Exp. Hematol. 3:213 (1975).PubMedGoogle Scholar
  20. 20.
    N.S. Wolf, The hemopoietic microenvironment, Clin. Haematol. 8:469 (1979).PubMedGoogle Scholar
  21. 21.
    M. Tavassoli and A. Friedenstein, Hemopoietic stromal micro-environment, Am. J. Hematol. 15:195 (1983).PubMedGoogle Scholar
  22. 22.
    T.D. Allen and T.M. Dexter, The essential cells of the hemopoietic microenvironment, Exp. Hematol. 12:517 (1984).PubMedGoogle Scholar
  23. 23.
    I.N. Rich, A role for the macrophage in normal hemopoiesis. I. Functional capacity of bone-marrow-derived macrophages to release hemopoietic growth factors, Exp. Hematol. 14:738 (1986).PubMedGoogle Scholar
  24. 24.
    S.C. Clark and R. Kamen, The human hematopoietic colony-stimulating factor, Science 236:1229 (1987).PubMedGoogle Scholar
  25. 25.
    D. Metcalf, Haemopoietic growth factors. Med. J. Austr. 148:516 (1988).Google Scholar
  26. 26.
    A. Billiau, J. Van Damme, G. Opdenakkar, W.E. Fibbe, J.H.F. Falkenburg, and J. Content, Interleukin 1 as cytokine inducer, Immunobiol. 172:323 (1986).Google Scholar
  27. 27.
    I.N. Rich, A role for the macrophage in normal hemopoiesis. II. Effect of varying physiological oxygen tensions on the release of hemopoietic growth factors from bone-marrow-derived macrophages in vitro. Exp. Hematol. 14:746 (1986).Google Scholar
  28. 28.
    G.C. Bagby, Production of multilineage growth factors by hematopoietic stromal cells: Intercellular regulatory network involving mononuclear phagocytes and interleukin-1, Blood Cells 13:147 (1987).PubMedGoogle Scholar
  29. 29.
    E.P. Cronkite, Analytical review of structure and regulation of hemopoiesis, Blood Cells 14:313 (1988).PubMedGoogle Scholar
  30. 30.
    J.E. Till and E.A. McCulloch, A direct measure of the radiation sensitivity of normal mouse bone marrow cells, Radiation Res. 14:213 (1961).PubMedGoogle Scholar
  31. 31.
    D.H. Pluznik and L. Sach, The cloning of normal mast cells in tissue culture, J. Cell. Comp. Physiol. 66:319 (1965).Google Scholar
  32. 32.
    T.R. Bradley and D. Metcalf, The growth of mouse bone marrow cells in vitro, Aust. J. Biol. Med. Sci. 44:287 (1966).Google Scholar
  33. 33.
    J.R. Stephenson, A.A Axelrad, D.L. McLeod, and M.M. Shreeve, Induction of colonies of hemoglobin synthesizing cells by erythropoietin in vitro. Proc. Natl. Acad. Sci. USA 68:1542 (1971).Google Scholar
  34. 34.
    D. Metcalf, G.T.V. Nossal, N.L. Warner, J.F. Miller, T.E. Mandel, J.E. Layton, G.A. Gutman, Growth of B-lymphocyte colonies in vitro. J. EXP. Med. 142:1534 (1975).Google Scholar
  35. 35.
    E. Gerassi and L. Sach, Regulation of the induction of colonies in vitro by normal human lymphocytes, Proc. Natl. Acad. Sci. USA 73:4546 (1976).PubMedGoogle Scholar
  36. 36.
    D. Metcalf, “The Molecular Control of Blood Cells”, Harvard University Press, Cambridge (1988).Google Scholar
  37. 37.
    B.I. Lord and N.G. Testa, The hemopoietic system: structure and regulation in “Hematopoiesis: Long-Term Effects of Chemotherapy and Radiation”, Nydia G. Testa and Robert Peter Gale eds., Marcel Dekker, New York (1988).Google Scholar
  38. 38.
    T.M. Dexter, T.D. Allen, L.G. Lajtha, R. Schofield, and B. I. Lord, Stimulation of differentiation of hemopoietic cells in vitro, J. Cell Physiol. 82:461 (1973).PubMedGoogle Scholar
  39. 39.
    T.M. Dexter, T.D. Allen, and L.G. Lajtha, Conditions controlling the proliferation of haemopoietic stem cells in vitro. J. Cell. Phvsiol. 91:335 (1977).Google Scholar
  40. 40.
    T.M. Dexter, N.G. Testa, T.D. Allen, T. Rutherford, and E. Scholnick The regulation of haemopoesis in long term bone marrow cultures, IV. Molecular and Cell Biological Aspects of erythropoiesis, Blood 58:699 (1981).PubMedGoogle Scholar
  41. 41.
    T.J. Haley “Nuclear Hematology”, Academic Press, New York (1965).Google Scholar
  42. 42.
    C.F. Baxter, E.H. Belchar, E.B. Harris, and L.F. Lamerton, Anaemia and erythropoiesis in the irradiated rat: an experimental study with particular reference to techniques involving radioactive iron, Br. J. Haematol. 1:86 (1955).PubMedGoogle Scholar
  43. 43.
    R.J. Cole and J. Paul, The effects of erythropoietin on haem synthesis in mouse yolk sac and cultured foetal liver cells, J. Embrvol. Exp. Morph. 15:245 (1966).Google Scholar
  44. 44.
    W.R. Bruce and E.A. McCulloch E.A., The effects of erythropoietic stimulation on the hemopoietic colony-forming cells of mice, Blood 23:216 (1964).PubMedGoogle Scholar
  45. 45.
    E. Filmanowicz and C.W. Gurney, Studies on erythropoiesis. XVI. Response to a single dose of erythropoietin in polycythemic mice. J. Lab. Clin. Med. 57:65 (1961).PubMedGoogle Scholar
  46. 46.
    B.J. Payne, H.B. Lewis, T.E. Murchinson, and E.A. Hart, Hematology of laboratory animals, in: “Handbook of Laboratory Science, VIII,” E.C. Melby, Jr., and N.H. Altman, Eds. CRC Press, Cleveland (1976).Google Scholar
  47. 47.
    T. Bothwell, R. Charlton, J. Cook, and C. Finch “Iron metabolism in man”, Blackwell Scientific Publication, Oxford (1979).Google Scholar
  48. 48.
    E.W. Lee, J.J. Kocsis, and R. Snyder, Acute effect of benzene on [59Fe] incorporation into circulating erythrocytes, Toxicol. Appl. Pharmacol. 27:431 (1974).PubMedGoogle Scholar
  49. 49.
    E.W. Lee, J.J. Kocsis, and R. Snyder, The use of ferrokinetics in the study of experimental anemia, Env. Health Perspect. 39:29 (1981).Google Scholar
  50. 50.
    C.A. Snyder, B. Goldstein, A. Sellakumar, and R.E. Albert, Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene, Am. J. Ind. Med. 5:429 (1984).PubMedGoogle Scholar
  51. 51.
    E.W. Lee, J.J. Kocsis, and R. Snyder, Dose-dependent inhibition of [59Fe] incorporation into erythrocytes after a single dose of benzene, Res. Commun. Chem. Pathol. Pharmacol. 5:547 (1973).PubMedGoogle Scholar
  52. 52.
    L.E. Bolcsak and D.E. Nerland, Inhibition of erythropoiesis by benzene and benzene metabolites, Toxicol. Appl. Pharmacol. 69:363 (1983).PubMedGoogle Scholar
  53. 53.
    R. Snyder, E. Dimitriadis, R. Guy, P. Hu, K. Cooper, H. Bauer, G. Witz, and B.D. Goldstein, Studies on the mechanism of benzene toxicity, Environ. Health Perspect. 82:31 (1989).PubMedGoogle Scholar
  54. 54.
    R.D. Irons, H.D. Heck, B.J. Moore, and K.A. Muirhead, Effects of short-term benzene administration on bone marrow cell cycle kinetics in rats, Toxicol. Appl. Pharmacol. 51:399 (1979).PubMedGoogle Scholar
  55. 55.
    E.M. Uyeki, A.E. Askar, D.W. Shoeman, and T.U. Bisel, Acute toxicity of benzene inhalation to hemopoietic precursor cells, Toxicol. Appl. Pharmacol. 40:49 (1977).PubMedGoogle Scholar
  56. 56.
    D. Gill, V. Jenkins, R. Kempen, and S. Ellis, The importance of pluripotent stem cells in benzene toxicity, Toxicology 16:163 (1980).PubMedGoogle Scholar
  57. 57.
    J.D. Green, C.A. Snyder, J. I. Obue, B.D. Goldstein, and R.E. Albert, Acute and chronic dose/response effects of inhaled benzene on multipotential hemopoietic stem (CFU-S) and granulocyte/macrophage progenitor (GM CFU-C) cells in CD-I mice, Toxicol. Appl. Pharmacol. 58:492 (1981).PubMedGoogle Scholar
  58. 58.
    K. Harigaya, M.E. Miller, E.P. Cronkite, and R.T. Drew, The detection of in vivo liquid bone marrow cultures, Toxicol. Appl. Pharmacol. 60:346 (1981).PubMedGoogle Scholar
  59. 59.
    E.P. Cronkite, T. Inoue, A.L. Carsten, M.E. Miller, J.E. Bullis, and R.T. Drew, Effects of benzene inhalation on murine pluripotent stem cells, J. Toxicol. Environ. Health 9:441 (1982).Google Scholar
  60. 60.
    A. Tunek, T. Olofsson, and M. Berlin, Toxic effects of benzene and benzene metabolites on granulopoietic stem cells and bone marrow cellularity in mice, Toxicol. Appl. Pharmacol. 59:149 (1981).PubMedGoogle Scholar
  61. 61.
    K. Toft, T. Olofsson, A. Tunek, and M. Berlin, Toxic effects on mouse bone marrow caused by inhalation of benzene, Arch. Toxicol. 51:295 (1982).Google Scholar
  62. 62.
    K. Baarson, C.A. Snyder, and R.E. Albert, Repeated exposures of C57B16 mice to 10 ppm inhaled benzene markedly depressed erythropoietic colony formation, Toxicol. Lett. 20:337 (1984).PubMedGoogle Scholar
  63. 63.
    V.N. Frash, B.G. Yushov, A.V. Karaulov, and V.L. Skuratov, Mechanism of action of benzene on hematopoiesis. Investigation of hematopoietic stem cells, Bull. Exp. Biol. Med. 82:985 (1976).Google Scholar
  64. 64.
    K.W. Gaido and D. Weirda, Modulation of stromal cell function in DBA/2J and B6C3F1 mice exposed to benzene or phenol, Toxicol. Appl. Pharmacol. 81:469 (1985).PubMedGoogle Scholar
  65. 65.
    K.W. Gaido and D. Weirda, In vitro effects of benzene metabolites on mouse bone marrow stromal cells, Toxicol. Appl. Pharmacol. 76:45 (1984).PubMedGoogle Scholar
  66. 66.
    K.W. Gaido and D. Wierda, Suppression of bone marrow stromal cell function by benzene and hydroquinone is ameliorated by indomethacin, Toxicol. Appl. Pharmacol. 89:378 (1987).PubMedGoogle Scholar
  67. 67.
    S.J. Pirozzi, M. Schlosser, and G.F. Kalf, Prevention of benzene induced myelotoxicity and prostaglandin synthesis in bone marrow of mice by inhibitors of prostaglandin H synthetase, Immunopharmacol. 18:39 (1989).Google Scholar
  68. 68.
    R.D. Irons and D.A. Neptun, Effects of principle hydroxy-metabolites of benzene on microtubule polymerization, Arch. Toxicol. 45:297 (1980).PubMedGoogle Scholar
  69. 69.
    K. Mann, M. Giesel, H. Fasold, W. Haase, Isolation of native microtubules from porcine brain and characterization at the GTP binding sites, FEBS Lett. 92:45 (1974).Google Scholar
  70. 70.
    R.W. Pfiefer and R.D. Irons, Alteration of lymphocyte function by quinones through sulfhydryl-dependent disruption of microtubule assembly, Int. J. Immunopharmacol. 5:463 (1983).Google Scholar
  71. 71.
    C. Schwartz, R. Snyder, and G. Kalf, The inhibition of mitochondrial DNA replication. in vitro by metabolites of benzene, hydroquinone and p-benzoquinone, Chem-Biol. Interact. 53:327 (1986).Google Scholar
  72. 72.
    W.K. Lutz and C.H. Schlatter, Mechanism of the carcinogenic action of benzene:irreversible binding to rat liver DNA, Chem-Biol. Interact. 18:241 (1977).PubMedGoogle Scholar
  73. 73.
    D.P. Gill and A. Ahmed, Covalent binding of [14C]benzene to cellular organelles and bone marrow nucleic acids, Pharmacol. 30:1127 (1981).Google Scholar
  74. 74.
    G.F. Kalf, T.R. Rushmore, and R. Snyder, Benzene inhibits RNA synthesis in mitochondria from liver and bone marrow, Chem-Biol. Interact. 42:353 (1982).PubMedGoogle Scholar
  75. 75.
    T. Rushmore, R. Snyder, and G. Kalf, Covalent binding of benzene and its metabolites to DNA in rabbit bone marrow mitochondria in vitro. Chem.-Biol. Interact. 49:133 (1984).PubMedGoogle Scholar
  76. 76.
    L. Jowa, G. Witz, R. Snyder, S. Winkle and G. Kalf, Synthesis and characterization of deoxyguanine-benzoquinone adducts, J. Appl. Toxicol. 10:47 (1990).PubMedGoogle Scholar
  77. 77.
    E.C. Vigliani and G. Saita, Benzene and leukemia, N. Engl. J. Med. 271:872 (1964).PubMedGoogle Scholar
  78. 78.
    M. Aksoy, H. Dincal, T. Akgun. S. Erdem, and G. Dincol, Hematological effects of chronic benzene poisoning in 217 workers, Br. J. Ind. Med. 28:296 (1971).PubMedGoogle Scholar
  79. 79.
    M. Aksoy, S. Erdem, and G. Dinol, Leukemia in shoe workers exposed chronically to benzene, Blood 44:837 (1974).PubMedGoogle Scholar
  80. 80.
    E. Vigliani and A. Forni, Benzene and leukemia, Environ. Res. 11:122 (1976).PubMedGoogle Scholar
  81. 81.
    B.D. Goldstein, Hematotoxicity in humans in benzene toxicity, a critical evaluation, J. Toxicol. Environ. Health. Suppl. 2:69 (1977).Google Scholar
  82. 82.
    J.-L. Amiel, Essai negtif d’induction de leuce mies chez les souris par le benzene, Rev. Fr. Etud. Clin. Biol. 5:198 (1960).PubMedGoogle Scholar
  83. 83.
    J. Ward, J. Weisberger, R. Yamamoto, T. Benjanub, C. Brown, and E. Weisberger, Long term effects of benzene in C57B1/6N mice, Arch. Environ. Health 30:22 (1975).PubMedGoogle Scholar
  84. 84.
    C.A. Snyder, B.D. Goldstein, A.R. Sellakumar, I. Bromberg, S. Laskin, and R.E. Albert, The inhalation toxicology of benzene: incidence of hematopoietic neoplasms and hematotoxicity in AKR/J and C57B1/6J mice, Toxicol. Appl. Pharmacol. 54:323 (1980).PubMedGoogle Scholar
  85. 85.
    C. Maltoni and C. Scarnato, First experimental demonstration of the carcinogenic effects of benzene, Med. Lav. 5:352 (1981).Google Scholar
  86. 86.
    C. Maltoni, G. Cotti, L. Valgimigli, and A. Mandrioli, Zymbal gland carcinomas in rats following exposure to benzene by inhalation, Am. J. Ind. Med. 3:11 (1982).PubMedGoogle Scholar
  87. 87.
    E.P. Cronkite, J.E. Bullis, T. Inoue, and R.T. Drew, Benzene inhalation produces leukemia in mice, Toxicol. Appl. Pharmacol. 75:358 (1984).PubMedGoogle Scholar
  88. 88.
    E.P. Cronkite, R.T. Drew, T. Inoue, and J.E. Bullis, Benzene hematotoxicity and leukemogenes is, Am. J. Ind. Med. 7:447 (1985).PubMedGoogle Scholar
  89. 89.
    E.P. Cronkite, Benzene hematotoxicity and leukemogenesis, Blood Cells 12:129 (1986).PubMedGoogle Scholar
  90. 90.
    E.P. Cronkite, Chemical leukemogenesis: benzene as a model, Hematol. 24:2 (1987).Google Scholar
  91. 91.
    B.J. Dean, Recent findings on the genetic toxicology of benzene, toluene, xylenes, and phenol, Mut. Res. 154:153 (1985).Google Scholar
  92. 92.
    B.J. Dean, Genetic toxicology of benzene, toluene, xylene and phenols, Mut. Res. 47:75 (1978).Google Scholar
  93. 93.
    A.M. Forni, A. Capellini, E. Pacifico, and E.C. Vigliani, Chromosome changes and their evolution in subjects with past exposure to benzene, Arch. Environ. Health 23:385 (1971).PubMedGoogle Scholar
  94. 94.
    H.G.S. Van Raalte and P. Grasso, Hematological myelotoxic, clastogenic, carcinogenic, and leukemogenic effects of benzene, Regulat. Toxicol. Pharmacol. 2:153 (1982).Google Scholar
  95. 95.
    R.R. Tice, T.F. Vogt, and D.L. Costa, Cytogenetic effects of inhaled benzene in murine bone marrow in Genotoxic Effect of Airborne Agents, Environ. Sci. Res. 25:257 (1982).Google Scholar
  96. 96.
    M. Hite, M. Pecharo, I. Smith, and S. Thornton, The effect of benzene in micronucleus test, Mut. Res. 77:149 (1980).Google Scholar
  97. 97.
    M.A. Diaz, J. Reiser, and J. Diez, Studies on benzene mutagenesis, I. The micronucleus test, Experientia 36:297 (1980).PubMedGoogle Scholar
  98. 98.
    C.A. Luke, R.R. Tice, and R.T. Drew, Duration and regimen induced micronuclei in the peripheral blood of mice exposed chronically to benzene, Environ. Mutagen. 7 Suppl.(3): 29, (1985).Google Scholar
  99. 99.
    S.J. Pirozzi, J.F. Renz, and G.F. Kalf, The prevention of benzene-induced genotoxicity in mice by indomethacin, Mut. Res. 222:291 (1989).Google Scholar
  100. 100.
    M.M. Gad-ElKarim, V.M.S. Ramanujam, and M.S. Legator, Correlation between the induction of micronuclei in bone marrow by benzene exposure and the excretion of metabolites in urine of CD-1 Mice, Toxicol. Appl. Pharmacol. 85:464 (1986).Google Scholar
  101. 101.
    T.A. Kirley, B.D. Goldstein, W.M. Maniaraand G. Witz, Metabolism of trans, trans-muconaldehyde, a microsomal hematotoxic metabolite of benzene, bu purified yeast aldehyde dehydrogenase and a mouse liver soluble fraction, Toxicol. Appl. Pharmacol. 100:360 (1989).PubMedGoogle Scholar
  102. 102.
    G.L. Erexson, J.L. Wilmer, W.H. Steinhagen, and A.D. Kligerman, Induction of cytogenic damage in rodents after short-term inhalation of benzene, Environ. Mut. 8:29 (1986).Google Scholar
  103. 103.
    M.N. Winternitz and A.D. Hirschfelder, Studies upon experimental pneumonia in rabbits: Part I-III, J. Exp. Med. 17:657–664. 1913.PubMedGoogle Scholar
  104. 104.
    A.D. Hirschfelder and M.C. Winternitz, Studies upon experimental pneumonia in rabbits. Part IV. Is there a parallelism in trypanocidal and pneumoccoccidal action of drugs?, J. Exp. Med. 17:666 (1913).PubMedGoogle Scholar
  105. 105.
    W.C. White and A.M. Gammon, The influence of benzol inhalation of experimental pulmonary tuberculosis in rabbits, Trans. Assoc. Amer. Physicians 29:332 (1914).Google Scholar
  106. 106.
    W.A. Camp and E.A. Baumgartner, Inflammatory reaction in rabbits with a severe leukopenia, J. Exp. Med. 22:174 (1915).PubMedGoogle Scholar
  107. 107.
    L. Hektoen, The effects of benzene on the production of antibodies, J. Infect. Dis. 19:69 (1916).Google Scholar
  108. 108.
    R. Smolik, K. Grzybek-Hryncewicz, A. Lange, and W. Zatonski, Serum complement levels in workers exposed to benzene, toluene, and xylene, Int. Arch. Arbeitsmed. 31:243 (1973).PubMedGoogle Scholar
  109. 109.
    A. Lange, R. Smolik, W. Zatonski, and J. Syzmanska, Serum immunoglobulin levels in workers exposed to benzene, toluene, and xylene, Int. Arch. Arbeitsmed. 32:37 (1973).Google Scholar
  110. 110.
    A. Lange, R. Smolik, W. Zatonski, and H. Glazman, Leukocyte agglutinins in workers exposed to benzene, toluene, and xylene, Int. Arch. Arbeitsmed. 31:45 (1973).PubMedGoogle Scholar
  111. 111.
    M.G. Rozen, C.A. Snyder, and R.E. Albert, Depression in B-and T-lymphocytes mitogen-induced blastogenesis in mice exposed to low concentrations of benzene, Toxicol. Lett. 20:343 (1984).PubMedGoogle Scholar
  112. 112.
    G.J. Rosenthal and C.A. Snyder, Modulation of the immune response to Listeria monocytogenes by benzene inhalation, Toxicol. Appl. Pharmacol. 80:502 (1985).PubMedGoogle Scholar
  113. 113.
    G.J. Rosenthal and C.A. Snyder, Inhaled benzene reduces aspects of cell-mediated tumor surveillance in mice, Toxicol. Appl. Pharmacol. 88:35 (1987).PubMedGoogle Scholar
  114. 114.
    D.L. Laskin, L. MacEachern, and R. Snyder, Activation of bone marrow phagocytes following benzene treatment of mice, Environ. Health Perspect. 82:75 (1989).PubMedGoogle Scholar
  115. 115.
    D.O. Adams and T.A. Hamilton, The cell biology of macrophage activation, Ann. Rev. Immunol. 2:283 (1984).Google Scholar
  116. 116.
    B.M. Babior, Oxidants from phagocytes. Agents of defense and destruction, Blood 64:959 (1984).PubMedGoogle Scholar
  117. 117.
    P.A. Ceruitti, Prooxidant states and tumor promotion, Science 227:375 (1985).Google Scholar
  118. 118.
    D.A. Eastmond, M.T. Smith, and R.D. Irons, An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure, Toxicol. Appl. Pharmacol. 91:85 (1987).PubMedGoogle Scholar
  119. 119.
    V. Subrahmanyam, A. Sadler, E. Suba, and D. Ross, Stimulation of in vitro bioactivation of hydroquinone by phenol in bone marrow cells, Drug Metab. Disp. 17:348 (1989).Google Scholar
  120. 120.
    G. Witz, S.R. Gondi, and B.D. Goldstein, Short-term toxicity of trans, trans muconaldehyde, Toxicol. Appl. Pharmacol. 80:511 (1985).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Suzanne Pirozzi Chatterjee
    • 1
  • Robert Snyder
    • 1
  1. 1.Department of Pharmacology and ToxicologyRutgers The State University of New JerseyPiscatawayUSA

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