Metabolic .beta.-hydroxylation and N-oxidation of n'-nitrosonornicotine

Abstract
3''-Hydroxy-N''-nitrosonornicotine (2),4''-hydroxy-N''-nitrosonornicotine (3) and N''-nitrosonornicotine 1-N-oxide (4) were synthesized and identified as metabolites in the F-344 rat of the tobacco-specific carcinogen N''-nitrosonornicotine (1). When 1 was incubated with liver microsomes from Aroclor-pretreated F-344 rats, trace amounts of 2 and 3 were produced and 4 was a major metabolite. The urine from rats treated with N''-nitrosonornicotine-2''-14C contained only trace amounts of 2 and 3, whereas 4 accounted for 6.7-9.4% of the dose.