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.

• Authors: U Andrae
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 118 Issue 2 Pg. 409-15 (Jan 30 1984) ISSN: 0006-291X [Print] United States
• PMID: 6704084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutagens
• Dexamethasone
• Cytochrome P-450 Enzyme System
• Methyl Methanesulfonate
• Oxygenases
• Hydroxyurea

Topics

• Animals
• Cell Differentiation
• Cell Line
• Cytochrome P-450 Enzyme System
• DNA Repair (drug effects, radiation effects)
• DNA Replication (drug effects, radiation effects)
• Dexamethasone (pharmacology)
• Enzyme Induction
• Hydroxyurea (metabolism, toxicity)
• Liver Neoplasms, Experimental (enzymology)
• Methyl Methanesulfonate (pharmacology)
• Mutagens
• Oxygenases (genetics)
• Rats
• Ultraviolet Rays