Metabolic Activation and Carcinogenesis of Tobacco-Specific Nitrosamine N'-Nitrosonornicotine (NNN): A Density Function Theory and Molecular Docking Study.

ABSTRACT: N'-nitrosonornicotine (NNN) is one of the tobacco-specific nitrosamines (TSNAs) that exists widely in smoke and smokeless tobacco products. NNN can induce tumors in various laboratory animal models and has been identified by International Agency for Research on Cancer (IARC) as a human carcinogen. Metabolic activation of NNN is primarily initiated by cytochrome P450 enzymes (CYP450s) via 2'-hydroxylation or 5'-hydroxylation. Subsequently, the hydroxylating intermediates undergo spontaneous decomposition to generate diazohydroxides, which can be further converted to alkyldiazonium ions, followed by attacking DNA to form various DNA damages, such as pyridyloxobutyl (POB)-DNA adducts and pyridyl-N-pyrrolidinyl (py-py)-DNA adducts. If not repaired correctly, these lesions would lead to tumor f

SUBMITTER: Fan T 

PROVIDER: S-EPMC6352179 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature