Metabolism and DNA adduct formation of carcinogenic tobacco-specific nitrosamines found in smokeless tobacco products

Research output: Chapter in Book/Report/Conference proceedingChapter


Tobacco-specific nitrosamines are the most abundant strong carcinogens in smokeless tobacco products. This chapter focuses on three of the most important of these compounds: N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The carcinogenic activities of NNN, NNK, and NNAL are discussed, and the metabolic pathways of these carcinogens are presented. Specific metabolite biomarkers have been developed to assess exposure to tobacco-specific nitrosamines in smokeless tobacco users; these are presented and discussed. DNA and protein adduct formation by tobacco-specific nitrosamines are also summarized, based mainly on studies in laboratory animals.

Original languageEnglish (US)
Title of host publicationSmokeless Tobacco Products
Subtitle of host publicationCharacteristics, Usage, Health Effects, and Regulatory Implications
Number of pages16
ISBN (Electronic)9780128181591
ISBN (Print)9780128181584
StatePublished - Jan 21 2020

Bibliographical note

Funding Information:
The contributions of all members of the Hecht laboratory to the research described in this chapter and of M. Gerard O'Sullivan and his team for histopathological analysis of tumors induced by tobacco-specific nitrosamines are gratefully acknowledged. This chapter is dedicated to the memory of Dietrich Hoffmann, whose research on the harmful effects of tobacco products, including tobacco-specific nitrosamines, was inspirational. Funding was provided by the National Cancer Institute, mainly through grant CA-81301 and Cancer Center Support Grant 77598.


  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
  • Carcinogenicity
  • DNA adducts
  • Metabolism
  • N'-nitrosonornicotine (NNN)
  • Protein adducts
  • Smokeless tobacco
  • Tobacco-specific nitrosamines
  • Urinary metabolite biomarkers

Fingerprint Dive into the research topics of 'Metabolism and DNA adduct formation of carcinogenic tobacco-specific nitrosamines found in smokeless tobacco products'. Together they form a unique fingerprint.

Cite this