Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure.
In previous work, we determined that granulocytic (CFU-GM) and erythroid (CFU-E) progenitor cell populations exhibited disparate responses to short-term benzene exposures. We now report on work investigating possible mechanisms for these observed disparate responses. Mice were exposed to either air or 10 ppm benzene for 6 h/d X 5 d. Immediately after the last exposure, mice were injected, i.v., with either saline or hydroxyurea (HU). The dose of HU was sufficient to kill hematopoietic cells in or near S-phase of the cell cycle and sufficient to synchronize the surviving populations of hematopoietic cells. Three days after benzene exposure, CFU-E numbers had declined to 50% of control values while CFU-GM numbers were equal to control values at this time. The benzene exposures were sufficient to double the percentage of CFU-E in S-phase but produced no such increase among CFU-GM. During 3 days of recovery from benzene exposure and HU treatment, the CFU-E population expanded 30-fold while the CFU-GM population expanded less than 3-fold. Following benzene exposure and HU treatment, both progenitor cells produced elevated numbers of their respective progeny. When CFU-E from benzene-exposed mice were cultured with varying concentrations of erythropoietin (EPO), the response at maximal EPO concentration was 66% of the response by control CFU-E. This strongly suggests that the CFU-E populations from benzene-exposed mice had been depleted of cells in or near S-phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Dempster
A M
AM
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Snyder
C A
CA
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008811:Mice, Inbred DBA
D001554:Benzene