The definitions of the chemical classes in Cohort Concern (CoC) by Kroes and co-workers are based on broad structural alerts, particular for N-nitroso compounds?for which alert consists essentially N–N?O substructure without further refinement. Recent pharmaceutical recalls have focused presence dialkyl N-nitrosamine impurities, some exceptionally potent carcinogens?2 orders magnitude more than...

S-Nitrosylation, the addition of a nitrosyl group to cysteine thiols, regulates various protein functions to mediate nitric oxide (NO) bioactivity. Recent studies have demonstrated that selectivity in protein S-nitrosylation signaling pathways is conferred through transnitrosylation, a transfer of the NO group, between proteins via interaction. We previously demonstrated that sensitivity to act...

The mutagenicity of 4-methylnitrosamine-1-3-pyridyl-1-butanone (NNK), either alone or in combination with low dose alpha particle irradiation, was examined using the human-hamster hybrid (A(L)) cell assay. NNK induced a dose-dependent toxicity in A(L) cells. In combination with a 25 cGy dose of alpha particles, the induced survival fraction fell within the statistical range of the calculated va...

BACKGROUND Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo. METHODS Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, an...

Tobacco-specific nitrosamines are believed to play a significant role as causes of cancer in people who use tobacco products. Whereas the uptake of one tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, has been shown by analysis of its metabolites in urine, there are no published studies on urinary levels of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), and...