RELATIONSHIP BETWEEN CARCINOGENICITY AND INVITRO METABOLISM OF NITROSOMETHYLETHYLAMINE, NITROSOMETHYL-N-BUTYLAMINE, AND NITROSOMETHYL(2-PHENYLETHYL)AMINE LABELED WITH DEUTERIUM IN THE METHYL AND ALPHA-METHYLENE POSITIONS

Abstract

With the use of rat liver preparations, the in vitro microsomal metabolism of methylethylnitrosamine, methyl-n-butylnitrosamine and methyl(2-phenylethyl)nitrosamine labeled with deuterium in the methyl and .alpha.-methylene positions was compared with that of the parent (unlabeled) compounds. All 3 forms of the liver carcinogen methylethylnitrosamine are metabolized with 2 sets of kinetic constants. Examination of these kinetic constants suggests that both methylation and ethylation of cellular nucleophiles might be important in the carinogenic action of these nitrosamines. The esophageal carcinogen, methyl(2-phenylethyl)nitrosamine, gave only one set of kinetic constants during metabolism. The metabolism of the3 methylbutylnitrosamines gave results similar to that of the 3 methylethyl nitrosamines. Except for metabolism of d2-methylbutylnitrosamine to butyraldehyde, 2 sets of kinetic constants were found. Approximately equivalent amounts of methylating species were produced from d3-methylbutylnitrosamine and d0-methylbutylnitrosamine.