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. 1996 Dec;104(Suppl 6):1277–1282. doi: 10.1289/ehp.961041277

Hematopoietic effects of benzene inhalation assessed by long-term bone marrow culture.

N G Abraham 1
PMCID: PMC1469741  PMID: 9118906

Abstract

The strong and long-lasting hematotoxic effect after benzene exposure in vivo (300 ppm, 6 hr/day, 5 days/week for 2 weeks) was assessed in mice with bone marrow cells grown in long-term bone marrow culture (LTBMC). Bone marrow cultures initiated 1 day after the last benzene exposure did not produce adequate numbers of hematopoietic cells over 3 weeks, and, in most cases, no erythroid or myeloid clonogenic cells could be recovered. The adherent cell layer of these cultures had a lowered capacity for supporting in vitro hematopoiesis after the second seeding with normal bone marrow cells compared with control cultures. Two weeks after the last benzene exposure, body weight, hematocrit, bone marrow cellularity, and committed hematopoietic progenitor content (BFU-E and CFU-GM) were regenerated to normal or subnormal values, whereas hematopoiesis in LTBMC was very poor. Over 8 weeks, little or no significant committed progenitor production was observed. Treatment of mice exposed to benzene with hemin (three doses of 3 micrograms/g bw i.v. over 2 weeks for a total dose of 9 micrograms/g) partially overcame the toxic effect of benzene on the hematopoietic system as measured by the LTBMC method. Cultures from mice treated with hemin had a modest recovery of BFU-E and CFU-GM clonogenic potential after 5 to 6 weeks in LTBMC. In contrast, little or no recovery was obtained for the adherent cell layer clonogenic capacity, even after hemin treatment. These results clearly indicate a strong, long-lasting toxic effect on the bone marrow stroma and a limited recovery of hematopoietic potential by clonogenic cells of the nonadherent population after in vivo hemin treatment.

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Selected References

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  1. Abraham N. G., Bucher D., Niranjan U., Brown A. C., Lutton J. D., Distenfeld A., Ahmed T., Levere R. D. Microenvironmental toxicity of azidothymidine: partial sparing with hemin. Blood. 1989 Jul;74(1):139–144. [PubMed] [Google Scholar]
  2. Abraham N. G., Levere R. D., Lutton J. D. Eclectic mechanisms of heme regulation of hematopoiesis. Int J Cell Cloning. 1991 May;9(3):185–210. doi: 10.1002/stem.5530090304. [DOI] [PubMed] [Google Scholar]
  3. Andrews L. S., Sasame H. A., Gillette J. R. 3H-Benzene metabolism in rabbit bone marrow. Life Sci. 1979 Aug 13;25(7):567–572. doi: 10.1016/0024-3205(79)90550-2. [DOI] [PubMed] [Google Scholar]
  4. Brandt J., Srour E. F., van Besien K., Briddell R. A., Hoffman R. Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow. J Clin Invest. 1990 Sep;86(3):932–941. doi: 10.1172/JCI114795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chertkov J. L., Drize N. J., Gurevitch O. A., Udalov G. A. Hemopoietic stromal precursors in long-term culture of bone marrow: I. Precursor characteristics, kinetics in culture, and dependence on quality of donor hemopoietic cells in chimeras. Exp Hematol. 1983 Mar;11(3):231–242. [PubMed] [Google Scholar]
  6. Chertkov J. L., Jiang S., Lutton J. D., Levere R. D., Abraham N. G. Hemin stimulation of hemopoiesis in murine long-term bone marrow culture. Exp Hematol. 1991 Oct;19(9):905–909. [PubMed] [Google Scholar]
  7. Cronkite E. P., Bullis J., Inoue T., Drew R. T. Benzene inhalation produces leukemia in mice. Toxicol Appl Pharmacol. 1984 Sep 15;75(2):358–361. doi: 10.1016/0041-008x(84)90219-9. [DOI] [PubMed] [Google Scholar]
  8. Cronkite E. P. Chemical leukemogenesis: benzene as a model. Semin Hematol. 1987 Jan;24(1):2–11. [PubMed] [Google Scholar]
  9. Cronkite E. P., Inoue T., Carsten A. L., Miller M. E., Bullis J. E., Drew R. T. Effects of benzene inhalation on murine pluripotent stem cells. J Toxicol Environ Health. 1982 Mar;9(3):411–421. doi: 10.1080/15287398209530174. [DOI] [PubMed] [Google Scholar]
  10. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  11. Gaido K. W., Wierda D. Modulation of stromal cell function in DBA/2J and B6C3F1 mice exposed to benzene or phenol. Toxicol Appl Pharmacol. 1985 Dec;81(3 Pt 1):469–475. doi: 10.1016/0041-008x(85)90418-1. [DOI] [PubMed] [Google Scholar]
  12. Garnett H. M., Cronkite E. P., Drew R. T. Effect of in vivo exposure to benzene on the characteristics of bone marrow adherent cells. Leuk Res. 1983;7(6):803–810. doi: 10.1016/0145-2126(83)90074-7. [DOI] [PubMed] [Google Scholar]
  13. Green J. D., Snyder C. A., LoBue J., Goldstein B. D., Albert R. E. Acute and chronic dose/response effects of inhaled benzene on multipotential hematopoietic stem (CFU-S) and granulocyte/macrophage progenitor (GM-CFU-C) cells in CD-1 mice. Toxicol Appl Pharmacol. 1981 May;58(3):492–503. doi: 10.1016/0041-008x(81)90102-2. [DOI] [PubMed] [Google Scholar]
  14. Harigaya K., Miller M. E., Cronkite E. P., Drew R. T. The detection of in vivo hematotoxicity of benzene by in vitro liquid bone marrow cultures. Toxicol Appl Pharmacol. 1981 Sep 15;60(2):346–353. doi: 10.1016/0041-008x(91)90237-9. [DOI] [PubMed] [Google Scholar]
  15. Hotta T., Kato T., Maeda H., Yamao H., Yamada H., Saito H. Functional changes in marrow stromal cells in aplastic anaemia. Acta Haematol. 1985;74(2):65–69. doi: 10.1159/000206171. [DOI] [PubMed] [Google Scholar]
  16. Ibraham N. G., Friedland M. L., Levere R. D. Heme metabolism in erythroid and hepatic cells. Prog Hematol. 1983;13:75–130. [PubMed] [Google Scholar]
  17. Irons R. D., Heck H., Moore B. J., Muirhead K. A. Effects of short-term benzene administration on bone marrow cell cycle kinetics in the rat. Toxicol Appl Pharmacol. 1979 Dec;51(3):399–409. doi: 10.1016/0041-008x(79)90364-8. [DOI] [PubMed] [Google Scholar]
  18. Longacre S. L., Kocsis J. J., Witmer C. M., Lee E. W., Sammett D., Snyder R. Toxicological and biochemical effects of repeated administration of benzene in mice. J Toxicol Environ Health. 1981 Feb;7(2):223–237. doi: 10.1080/15287398109529974. [DOI] [PubMed] [Google Scholar]
  19. Lutton J. D., Ibraham N. G., Friedland M., Levere R. D. The toxic effects of heavy metals on rat bone marrow in vitro erythropoiesis: protective role of hemin and zinc. Environ Res. 1984 Oct;35(1):97–103. doi: 10.1016/0013-9351(84)90116-6. [DOI] [PubMed] [Google Scholar]
  20. Lutton J. D., Levere R. D., Abraham N. G. Physiologic role of heme and cytochrome P-450 in hematopoietic cells. Proc Soc Exp Biol Med. 1991 Mar;196(3):260–269. doi: 10.3181/00379727-196-43186a. [DOI] [PubMed] [Google Scholar]
  21. Marsh J. C., Chang J., Testa N. G., Hows J. M., Dexter T. M. The hematopoietic defect in aplastic anemia assessed by long-term marrow culture. Blood. 1990 Nov 1;76(9):1748–1757. [PubMed] [Google Scholar]
  22. Post G., Snyder R., Kalf G. F. Metabolism of benzene and phenol in macrophages in vitro and the inhibition of RNA synthesis by benzene metabolites. Cell Biol Toxicol. 1986 Jun;2(2):231–246. doi: 10.1007/BF00122692. [DOI] [PubMed] [Google Scholar]
  23. Reincke U., Rosenblatt M., Hellman S. Adherent stem cells: frequency in mouse marrow and terminal clone sizes in long-term culture. Exp Hematol. 1985 Jul;13(6):545–553. [PubMed] [Google Scholar]
  24. Rickert D. E., Baker T. S., Bus J. S., Barrow C. S., Irons R. D. Benzene disposition in the rat after exposure by inhalation. Toxicol Appl Pharmacol. 1979 Jul;49(3):417–423. doi: 10.1016/0041-008x(79)90441-1. [DOI] [PubMed] [Google Scholar]
  25. Rinsky R. A., Smith A. B., Hornung R., Filloon T. G., Young R. J., Okun A. H., Landrigan P. J. Benzene and leukemia. An epidemiologic risk assessment. N Engl J Med. 1987 Apr 23;316(17):1044–1050. doi: 10.1056/NEJM198704233161702. [DOI] [PubMed] [Google Scholar]
  26. Rozen M. G., Snyder C. A., Albert R. E. Depressions in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene. Toxicol Lett. 1984 Mar;20(3):343–349. doi: 10.1016/0378-4274(84)90170-x. [DOI] [PubMed] [Google Scholar]
  27. Seidel H. J., Barthel E., Zinser D. The hematopoietic stem cell compartments in mice during and after long-term inhalation of three doses of benzene. Exp Hematol. 1989 Mar;17(3):300–303. [PubMed] [Google Scholar]
  28. Seidel H. J., Beyvers G., Pape M., Barthel E. The influence of benzene on the erythroid cell system in mice. Exp Hematol. 1989 Aug;17(7):760–764. [PubMed] [Google Scholar]
  29. Snyder R., Lee E. W., Kocsis J. J., Witmer C. M. Bone marrow depressant and leukemogenic actions of benzene. Life Sci. 1977 Dec 15;21(12):1709–1721. doi: 10.1016/0024-3205(77)90149-7. [DOI] [PubMed] [Google Scholar]
  30. Thomas D. J., Reasor M. J., Wierda D. Macrophage regulation of myelopoiesis is altered by exposure to the benzene metabolite hydroquinone. Toxicol Appl Pharmacol. 1989 Mar 1;97(3):440–453. doi: 10.1016/0041-008x(89)90249-4. [DOI] [PubMed] [Google Scholar]
  31. Volin L., Ruutu T., Knuutila S., Tenhunen R. Heme arginate treatment for myelodysplastic syndromes. Leuk Res. 1988;12(5):423–431. doi: 10.1016/0145-2126(88)90062-8. [DOI] [PubMed] [Google Scholar]

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