Benzene-induced hematotoxicity and bone marrow compensation in B6C3F1 mice.
Long-term inhalation exposure of benzene has been shown to cause hematotoxicity and an increased incidence of acute myelogenous leukemia in humans. The progression of benzene-induced hematotoxicity and the features of the toxicity that may play a major role in the leukemogenesis are not known. We report the hematological consequences of benzene inhalation in B6C3F1 mice exposed to 1, 5, 10, 100, and 200 ppm benzene for 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 exposure to 10 ppm benzene or less. Exposure of mice to 100 and 200 ppm benzene reduced the number of total bone marrow cells, progenitor cells, differentiating hematopoietic cells, and most blood parameters. Replication of primitive progenitor cells in the bone marrow was increased during the exposure period as a compensation for the cytotoxicity induced by 100 and 200 ppm benzene. In mice exposed to 200 ppm benzene, the primitive progenitor cells maintained an increased percentage of cells in S-phase through 25 days of recovery compared with controls. The increased replication of primitive progenitor cells in concert with the reported genotoxicity induced by benzene provides the components necessary for producing an increased incidence of lymphoma in mice. Furthermore, we propose this mode of action as a biologically plausible mechanism for benzene-induced leukemia in humans exposed to high concentrations of benzene.
Farris
G M
GM
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA.
Robinson
S N
SN
Gaido
K W
KW
Wong
B A
BA
Wong
V A
VA
Hahn
W P
WP
Shah
R S
RS
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D006402:Hematologic Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016196:S Phase / Q000502:physiology; D013055:Spectrophotometry, Infrared; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects
D001973:Bromodeoxyuridine; D001554:Benzene