Abstract
The first evidence for the reductive metabolism of a noncyclic nitrosamine to the corresponding hydrazine derivative in vivo and in vitro is provided. Under anaerobic conditions, N-nitrosodiphenylamine was reduced by guinea pig liver 9000 g supernatant to 1,1-diphenylhydrazine in the presence of 2-hydroxypyrimidine or to acetaldehyde diphenylhydrazone in the presence of acetaldehyde. These metabolites were identified unequivocally by comparative study with authentic samples. In addition, the study shows that such reductive reactions of the nitrosamine can be catalyzed by guinea pig and rabbit liver aldehyde oxidase in the presence of its electron donors. When the nitrosamine was given orally to acetaldehyde-treated guinea pigs, a metabolite was detected from plasma and identified as acetaldehyde diphenylhydrazone by comparison with the authentic sample.
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