Metabolic fate of N-alkyl-N-(3-hydroxypropyl and 2-hydroxy-ethyl)nitrosamines in the rat in relation to the induction of bladder cancer by N-butyl-N-(4-hydroxybutyl)nitrosamine and its homologs.
The metabolic fate of N-alkyl-N-(3-hydroxypropyl)nitrosamines and N-alkyl-N-(2-hydroxyethyl)nitrosamines (alkyl=butyl, ethyl) [analogs of N-alkyl-N-(4-hydroxybutyl)nitrosamines, which are potent bladder carcinogens] was investigated in the rat in order to elucidate a possible relationship between chemical structure, in vivo metabolism, and organotropic carcinogenicity to the urinary bladder of N-alkyl-N-(4-hydroxybutyl)nitrosamines. The principal urinary metabolites of N-alkyl-N-(3-hydroxypropyl)nitrosamines and N-alkyl-N-(2-hydroxyethyl)nitrosamines, which are not carcinogenic to the urinary bladder but are hepato-carcinogenic in rats, were the corresponding 2-carboxyethyl and carboxymethyl compounds. Urinary metabolites with a 2-carboxyethyl or carboxymethyl group are not important, as far as the induction of bladder cancer is concerned, and the urinary excretion of metabolites having a 3-carboxypropyl chain is essential for the induction of bladder cancer.
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004052:Diethylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009602:Nitrosamines / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000378:metabolism
D009602:Nitrosamines; C023845:N-ethyl-N-hydroxyethylnitrosamine; D002085:Butylhydroxybutylnitrosamine; D004052:Diethylnitrosamine; C006858:butyl(3-hydroxypropyl)nitrosamine; C006857:butyl(2-hydroxyethyl)nitrosamine; C032049:N-ethyl-N-(3-hydroxypropyl)nitrosamine