Evidence for the involvement of cytochrome P-450-dependent monooxygenase(s) in the formation of genotoxic metabolites from N-hydroxyurea

Abstract

Hydroxyurea induces DNA repair replication in the cytochrome P-450-containing C2Rev7 rat hepatoma cell line. Repair is severalfold increased by pretreatment of the cells with dexamethasone, which induces cytochrome P-450-dependent monooxygenase activities in these cells. In the dedifferentiated hepatoma line H5, which strongly expresses cytochrome P-448 but no cytochrome P-450-dependent enzyme activities, hydroxyurea is not genotoxic. The results support the notion that the formation of genotoxic metabolites from hydroxyurea is mediated by a cytochrome P-450-dependent enzyme.