title: 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).
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, O(6)-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.
authors.affiliation: The Masonic Cancer Center, University of Minnesota , MMC 806, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455, United States.
authors.forename: Silvia
authors.initials: S
authors.lastname: Balbo
authors.forename: Pramod
authors.initials: P
authors.lastname: Upadhyaya
authors.forename: Peter W
authors.initials: PW
authors.lastname: Villalta
authors.forename: Xuemin
authors.initials: X
authors.lastname: Qian
authors.forename: Fekadu
authors.initials: F
authors.lastname: Kassie
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts; D005260:Female; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D051379:Mice; D009602:Nitrosamines / Q000633:toxicity*; D013234:Stem Cells / Q000378:metabolism*; D014026:Nicotiana
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D000444:Aldehyde Dehydrogenase