RESUMO
The metabolism of N-nitrosobis(2-oxopropyl)amine (BOP) was examined in microsomes from uninduced F-344 rats. Even when the conditions were varied, no metabolism of this compound was detected. On the other hand, freshly isolated hepatocytes from F-344 rats metabolized BOP efficiently to CO2. The kinetics of conversion showed there were at least two components. The high affinity component had a Km of 0.13 mM while the lower had a Km of 1.3 mM. As products of the metabolism, N-nitroso(2-hydroxypropyl)(2-oxopropyl)-amine (HPOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP) were found whereas little acetol and no N-nitrosomethyl-2-oxopropylamine (MOP) were detected.
Assuntos
Carcinógenos/metabolismo , Fígado/metabolismo , Microssomos Hepáticos/metabolismo , Nitrosaminas/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344RESUMO
N-nitrosomethylaniline, an esophageal carcinogen in the rat, was inactive in the Ames mutagenicity assay under all conditions examined. However, various ring-substituted N-nitrosomethylanilines were found to be mutagenic; some of these did not require activation. No correlation could be found between the rate of demethylation or substituent effects of the ring-substituted N-nitrosomethylanilines and mutagenic potency. The protein concentration and levels of aryl hydrocarbon hydroxylase in the liver S9 fraction were determined to be poor indices of the ability of S9 to activate nitrosamines to their mutagenic metabolites.