DNA ADDUCT FORMATION IN THE BONE-MARROW OF B6C3F1 MICE TREATED WITH BENZENE

We used P-1-enhanced P-32-postlabeling to investigate DNA adduct forma tion in the bone marrow of B6C3F1 mice treated intraperitoneally with benzene (BZ). No adducts were detected in the bone marrow of controls or mice treated,vith various doses of BZ once a day, After twice-daily treatment with BZ, 440 mg/kg, for 1 to 7 days, one major and two mino r DNA adducts were detected, The relative adduct levels ranged from 0. 06-1.46 x 10(-7). In vitro treatment of bone marrow from B6C3F1 mice w ith various doses of hydroquinone (HQ) for 24 h also produced three DN A adducts, These adducts were the same as those formed after in vivo t reatment of bone marrow with BZ, Cochromatography experiments indicate d that the principal DNA adduct detected in the bone marrow of B6C3F1 mice was the same as that detected in HL-60 cells treated with HQ. Thi s finding suggests that HQ may be the principal metabolite of BZ leadi ng to DNA adduct formation in vivo. DNA adduct 2 corresponds to the DN A adduct formed in HL-60 cells treated with 1,2,4-benzenetriol, DNA ad duct 3 remains unidentified, After a 7-day treatment with BZ, 440 mg/k g twice a day, the number of cells per femur decreased from 1.6 X 10(7 ) to 0.85 X 10(7), indicating myelotoxicity, In contrast, administrati on of BZ once a day produced only a small decrease in bone marrow cell ularity. These studies demonstrate that metabolic activation of BZ lea ds to the formation of DNA adducts in the bone marrow, Further investi gation is required to determine the role of DNA adducts and other form s of DNA damage in the myelotoxic effects of exposure to BZ.