4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N¢-nitrosonornicotine (NNN) are two tobacco smoke nitrosamines. NNK induces lung tumors and NNN causes esophageal tumors in laboratory animals. Both are listed as human carcinogens by the International Agency for Research on Cancer. NNK and NNN require hydroxylation adjacent to the nitrosamine group to exert their genotoxic effects. They both generate a pyridyloxobutylating agent that generates a variety of adducts including 7-[4-3-(pyridyl)-4-oxobut-1-yl]-guanine (7-pobG), O6-[4-3-(pyridyl)-4-oxobut-1-yl]-guanine (O6-pobG), O2-[4-3-(pyridyl)-4-oxobut-1-yl]thymidine (O2-pobT), and O2-[4-3-(pyridyl)-4-oxobut-1-yl]-cytosine (O2-pobC). Mechanistic studies in cell lines and laboratory animals have provided important clues as to how these adducts contribute to the carcinogenic properties of NNK and NNN. This talk will review the highlights from 25 years of research on this subject.

The role of pyridyloxobutyl DNA adducts in the carcinogenic properties of tobacco specific nitrosamines

ACS Fall 2021

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