DNA adducts in aldehyde dehydrogenase-positive lung stem cells of A/J mice treated with the tobacco specific lung carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)

Silvia Balbo, Pramod Upadhyaya, Peter W. Villalta, Xuemin Qian, Fekadu Kassie

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Abstract

Lung cancer is the leading cause of cancer death in the world. Evidence suggests that lung cancer could originate from mutations accumulating in a subpopulation of self-renewing cells, lung stem cells. Aldehyde dehydrogenase (ALDH) is a marker of stem cells. To investigate the presence of DNA modifications in these cells, we isolated ALDH-positive lung cells from A/J mice exposed to the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Using LC-NSI-HRMS/MS-PRM, O6-methyl-G, 7-POB-G, and O 2-POB-dT were positively identified in ALDH-positive cell DNA. This is the first example of detection of carcinogen-DNA adducts in lung stem cells, supporting the hypothesis of their role in lung carcinogenesis.

Original languageEnglish (US)
Pages (from-to)511-513
Number of pages3
JournalChemical research in toxicology
Volume26
Issue number4
DOIs
StatePublished - Apr 15 2013

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