DNA adduct formation from tobacco-specific N-nitrosamines

摘要: Tobacco-specific N-nitrosamines are a group of carcinogens derived from the tobacco alkaloids. They likely causative factors for cancers lung, esophagus, pancreas, and oral cavity in people who use products. The most carcinogenic tobacco-specific nitrosamines laboratory animals 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN). DNA adduct formation NNK NNN has been studied extensively is reviewed here. metabolically activated by cytochromes P450 to intermediates which methylate pyridyloxobutylate DNA. resulting adducts have detected cells tissues susceptible carcinogenesis rodents. methylation pyridyloxobutylation pathways both important NNK. also induces single strand breaks increases levels 8-oxodeoxyguanosine treated animals. NNAL, like potent pulmonary carcinogen, methylating pyridyloxobutylating intermediates. pyridyloxobutylates its rat target tissues, esophagus nasal mucosa. Methyl pyridyloxobutyl human tissues. methyl result part exposure smokers NNK, but these non-smokers. Some non-smokers may be due environmental smoke exposure. There potential dietary endogenous sources adducts. Pyridyloxobutyl mainly N-nitrosamines. In animals, carcinogenicity closely correlated many instances, it that similar relationships will hold humans.