HIGH INDUCIBILITY OF MOUSE RENAL CYP2E1 GENE BY TOBACCO-SMOKE AND ITSPOSSIBLE EFFECT ON DNA SINGLE-STRAND BREAKS

Several studies have shown in humans an association between renal carc inoma and cigarette smoking. Cigarette smoke contains numerous cytochr ome P450 inducers and substrates. In the present study we investigated the effect of cigarette smoke on the regulation of murine cytochrome P450 expression in kidney and its possible role in the induction of si ngle strand breaks of DNA. Results demonstrated that CYP2E1 (activity, protein, and mRNA) was induced by tobacco smoke (2.1, 5.6, and 20.8, respectively). We did not detect any CYP1A, CYP2B, and CYP3A using Wes tern blot and RT-PCR experiments. We have analyzed the renal single st rand breaks of DNA in control and treated mice. The results indicated an increase of single strand breaks of DNA in kidney from treated mice which paralleled the high inducibility of the CYP2E1. No significant difference was observed between lymphocytes (which expressed very low or undetectable cytochrome P450 levels) of control and treated mice. ( C) 1996 Academic Press, Inc