Microsome- and hepatocyte-mediated mutagenicity of hydroxyurea and related aliphatic hydroxamic acids in V79 Chinese hamster cells.
The potential of N-hydroxyurea to induce gene mutations in V79 Chinese hamster cells was investigated. Upon metabolic activation by liver microsomes from phenobarbital-treated rats or by isolated rat hepatocytes co-cultured with the V79 cells, hydroxyurea caused a concentration-dependent increase in the frequency of HGPRT-deficient mutants. Hydroxyurea was not mutagenic in the absence of metabolic activation. Addition of catalase inhibited microsome-mediated mutagenicity, indicating that hydrogen peroxide was involved in the formation of the mutagenic DNA lesion. Acetohydroxamic acid and N-hydroxyurethane also induced hepatocyte-mediated mutagenicity, suggesting that the potential to elicit metabolism-dependent mutagenicity may be a common property of aliphatic hydroxamic acids.
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006877:Hydroxamic Acids / Q000378:metabolism / Q000633:toxicity*; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006877:Hydroxamic Acids; D009153:Mutagens; D006918:Hydroxyurea; D010634:Phenobarbital