Metabolism of N-nitrodialkylamines.
The in-vitro and in-vivo metabolism of N-nitramines was investigated to compare it with that of N-nitrosamines. N-Nitrodibutylamine and N-nitrodiethylamine were incubated with rat liver microsomes and hepatocytes, and the products were analysed by high-performance liquid chromatography and gas-liquid chromatography. The in-vitro metabolic pattern of these N-nitramines was similar to that of the corresponding N-nitrosamines, except that N-nitromonoalkylamines (produced by alpha-hydroxylation) were isolated and identified after incubation of N-nitrodialkylamines. Seven N-nitramines, including glucuronides, were isolated and identified from urine of rats given N-nitrodibutylamine, produced by omega, omega-1, and alpha oxidations of the N-nitramine. The in-vivo metabolic pattern of N-nitrodibutylamine was also similar to that of N-nitrosodi-n-butylamine except that N-nitromonobutylamine (a product of alpha-hydroxylation) was isolated and identified. N-Nitramines were mutagenic to Escherichia coli WP2 hcr-, but not to Salmonella typhimurium TA 1535. N-Nitrodibutylamine and N-nitrodiethylamine were mutagenic only in the presence of hepatic microsomes, while N-nitromonobutylamine and N-nitromonoethylamine were direct mutagens. Thus, the N-nitrodialkylamine is also metabolically activated to a mutagen through an alpha-hydroxylation.
D000818:Animals; D002082:Butylamines / Q000378:metabolism* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D004048:Diethylamines / Q000378:metabolism* / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D002082:Butylamines; D004048:Diethylamines; D009153:Mutagens; C045280:N-nitrodibutylamine; C031406:N-nitrodiethylamine