Relationship between oxidative metabolites of hydrazine and hydrazine-induced mutagenicity.
Hydrazine (Hz) mutagenicity was observed in a test using Escherichia coli B/r strain, WP2 uvrA and was enhanced by the addition of rat liver microsomal fraction containing a generating system, while the enhanced mutagenicity was diminished by the addition of metyrapone to the microsome-free levels. On the other hand, an NADPH-dependent difference spectrum of the metabolic intermediate of Hz-complex, characterized by a maximum level of 448 nm, was also inhibited by metyrapone. The results show that the oxidative intermediates, which are diimide and its precursor, hydrazine free radical [Biochem. Biophys. Res. Commun., 133 (1986) 1086], are responsible not only for hepatotoxicity but also for the enhancement of genotoxicity or mutagenicity.
D000818:Animals; D004926:Escherichia coli; D006834:Hydrazines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006834:Hydrazines; D009153:Mutagens; C029424:hydrazine; D010634:Phenobarbital; D008797:Metyrapone