EFFECTS OF SHORT-TERM BENZENE ADMINISTRATION ON BONE-MARROW CELL-CYCLE KINETICS IN THE RAT

Hematology, cell cycle phase, and [3H]thymidine ([3H]TdR) uptake and retention in bone marrow were studied in male Fischer-344 rats exposed to benzene by repeated subcutaneous injection (0.5 or 1.0 ml benzene/kg/day). Peripheral lymphocytes and differentiating bone marrow precursor cells were found to be the most sensitive cell populations following repeated benzene administration. Benzene exposure resulted in an increase in the relative number of bone marrow precursor cells in G2 or M phase of the cell cycle as determined by laser-based flow cytofluorometry. Benzene treatment resulted in an increase in cell proliferative activity as determined by both cytofluorometry and [3H]TdR uptake. Although the uptake of [3H]TdR into DNA was initially higher in animals repeatedly exposed to benzene than in controls, paralleling the increase in cell proliferative index, the specific activity of DNA rapidly decreased, suggesting a defect in maturation among affected precusor cells. A general inhibition of DNA synthesis in bone marrow was not observed. It would appear that benzene-induced cytotoxicity in bone marrow is a function of both cell differentiation and cell cycle phase. © 1979.