BENZENE-INDUCED GENOTOXICITY IN MICE IN-VIVO DETECTED BY THE ALKALINECOMET ASSAY - REDUCTION BY CYP2E1 INHIBITION

The myelotoxic and genotoxic effects of benzene have been related to o xidative DNA damage after metabolism by CYP2E1. Single cell gel electr ophoresis (alkaline comet assay) detects DNA damage and may thus be a convenient method for the study of benzene genotoxicity. Benzene expos ure to NMRI mice as a single oral gavage at 40, 200 or 450 mg/kg resul ted in dose-related DNA damage indicated by an increased comet tail le ngth of peripheral blood lymphocytes and bone marrow nucleated cells s ampled 6 h after exposure. After a dose of 40 mg/kg, there was a 1.6-f old increase of 'tail length' in bone marrow nucleated cells in compar ison with the control (p < 0.01). There was no significant increase in DNA damage in peripheral blood lymphocytes in the same animals. At 20 0 mg/kg, the tail length was 4.8-fold and 4.0-fold increased in the tw o cell types, respectively (p < 0.01). At 450 mg/kg, the tail length w as further increased to 5.4-fold and 6.6-fold of the control values, r espectively (p < 0.01). Pretreatment with propylene glycol (5 mu l/g b .wt., twice with a 60-min interval), a selective CYP2E1 inhibitor, red uced the increase in the tail length by about half at all doses in bot h cell types(p < 0.01). By comparing our data with those from genotoxi city studies on benzene using other methods, we conclude that the 'alk aline comet assay' is a sensitive method to detect DNA damage induced by benzene. We also infer that CYP2E1 contributes, at least partly, to the formation of the 'comet'-inducing metabolites in the chosen cell types.