title: Induction of sister chromatid exchanges and cell division delays in human lymphocytes by microsomal activation of benzene.
abstract: Metabolic activation of benzene by rat liver microsomes and a reduced nicotinamide adenine dinucleotide phosphate-generating system (S-9 mix) induced sister chromatid exchanges (SCEs) and cell division delays in cultured human lymphocytes. There were optimal concentrations of S-9 mix for the conversion of benzene into the active metabolites that exerted these cytotoxic effects. Reduced glutathione prevented the induction of SCEs by benzene plus S-9 mix in a dose-dependent manner. Reduced glutathione (3 mM) also prevented the induction of SCEs by catechol or hydroquinone, active metabolites of benzene and potent inducers of SCEs, strongly suggesting that glutathione did not simply inhibit the activity of S-9 mix to activate benzene but actually prevented the production of DNA lesions by the active metabolites. Pulse treatment of cells with benzene plus S-9 mix produced the largest number of SCEs when administered at 40 hr of culture (fixed at 72 hr) but did not induce SCEs when administered immediately after the beginning of culture. This indicates that induced DNA lesions that could lead to formation of SCEs are removed in time.
mesh_terms: D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D001711:Biotransformation; D002455:Cell Division / Q000187:drug effects; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013997:Time Factors
chemical_list: D005978:Glutathione; D001554:Benzene