biostudies-literatureLi YNational Cancer InstituteNCI NIH HHS1004-1015https://www.ebi.ac.uk/biostudies/studies/S-EPMC11558792biostudies-literatureUnknown34(4)The International Agency for Research on Cancer has classified the tobacco-specific nitrosamines <i>N</i>'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as "carcinogenic to humans" (Group 1). To exert its carcinogenicity, NNN requires metabolic activation to form reactive intermediates which alkylate DNA. Previous studies have identified cytochrome P450-catalyzed 2'-hydroxylation and 5'-hydroxylation of NNN as major metabolic pathways, with preferential activation through the 5'-hydroxylation pathway in some cultured human tissues and patas monkeys. So far, the only DNA adducts identified from NNN 5'-hydroxylation in rat tissues are 2-[2-(3-pyridyl)-<i>N</i>-pyrrolidinyl]-2'-deoxyinosine (Py-Py-dI), 6-[2-(3-pyridyl)-<i>N</i>-pyrrolidinyl]-2'-deoxynebularChemical research in toxicologyInvestigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA by &lt;i&gt;N&lt;/i&gt;'-Nitrosonornicotine Metabolism.PMC11558792P30 CA077598R01 CA-81301R37 CA081301R01 CA081301P30 CA-077598Li YZarth ATHecht SSUpadhyaya PCarlson ESfalseInvestigation of 2'-Deoxyadenosine-Derived Adducts Specifically Formed in Rat Liver and Lung DNA by &lt;i&gt;N&lt;/i&gt;'-Nitrosonornicotine Metabolism.The International Agency for Research on Cancer has classified the tobacco-specific nitrosamines <i>N</i>'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as "carcinogenic to humans" (Group 1). To exert its carcinogenicity, NNN requires metabolic activation to form reactive intermediates which alkylate DNA. Previous studies have identified cytochrome P450-catalyzed 2'-hydroxylation and 5'-hydroxylation of NNN as major metabolic pathways, with preferential activation through the 5'-hydroxylation pathway in some cultured human tissues and patas monkeys. So far, the only DNA adducts identified from NNN 5'-hydroxylation in rat tissues are 2-[2-(3-pyridyl)-<i>N</i>-pyrrolidinyl]-2'-deoxyinosine (Py-Py-dI), 6-[2-(3-pyridyl)-<i>N</i>-pyrrolidinyl]-2'-deoxynebular2021-01-01T00:00:00Z2021 Apr2025-04-04T00:33:48.592Z2025-04-04T00:33:48.592ZS-EPMC115587923372070310.1021/acs.chemrestox.1c00012