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)

详细信息    查看全文

• 作者：Silvia Balbo ; Pramod Upadhyaya ; Peter W. Villalta ; Xuemin Qian ; Fekadu Kassie
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：April 15, 2013
• 年：2013
• 卷：26
• 期：4
• 页码：511-513
• 全文大小：171K
• 年卷期：v.26,no.4(April 15, 2013)
• ISSN：1520-5010

文摘

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鈥揘SI-HRMS/MS鈥揚RM, O⁶-methyl-G, 7-POB-G, and O²-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.