BENZENE-INDUCED HEMATOTOXICITY AND BONE-MARROW COMPENSATION IN B6C3F1MICE

Long-term inhalation exposure of benzene has been shown to cause hemat otoxicity and an increased incidence of acute myelogenous leukemia in humans. The progression of benzene-induced hematotoxicity and the feat ures of the toxicity that may play a major role in the leukemogenesis are not known. We report the hematological consequences of benzene inh alation in B6C3F1 mice exposed to 1, 5, 10, 100, and 200 ppm benzene f or 6 hr/day, 5 days/week for 1, 2, 4, or 8 weeks and a recovery group. There were no significant effects on hematopoietic parameters from ex posure to 10 ppm benzene or less. Exposure of mice to 100 and 200 ppm benzene reduced the number of total bone marrow cells, progenitor cell s, differentiating hematopoietic cells, and most blood parameters. Rep lication of primitive progenitor cells in the bone marrow was increase d during the exposure period as a compensation for the cytotoxicity in duced by 100 and 200 ppm benzene. In mice exposed to 200 ppm benzene, the primitive progenitor cells maintained an increased percentage of c ells in S-phase through 25 days of recovery compared with controls. Th e increased replication of primitive progenitor cells;in concertwith t he reported genotoxicity induced by benzene provides the components ne cessary for producing an increased incidence of lymphoma in mice. Furt hermore, we propose this mode of action as a biologically plausible me chanism for benzene-induced leukemia in humans exposed to high concent rations of benzene. (C) 1997 Society of Toxicology.