Evidence for the involvement of cytochrome P-450-dependent monooxygenase(s) in the formation of genotoxic metabolites from N-hydroxyurea.
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.
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D006918:Hydroxyurea / Q000378:metabolism* / Q000633:toxicity; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens; D010105:Oxygenases / Q000235:genetics*; D051381:Rats; D014466:Ultraviolet Rays
D009153:Mutagens; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D008741:Methyl Methanesulfonate; D010105:Oxygenases; D006918:Hydroxyurea