Lung cancer is the leading cause of cancer death in the world, causing more deaths than the next three most common cancers combined (colon, breast and prostate). Recent evidence suggests that human lung cancer, like other cancers, may originate from a small subset of self�renewing tumor cells known as cancer stem cells. These cells originate from normal stem cells that acquire mutations leading to loss of natural growth control mechanisms and expansion into a self�renewing pool of cancer stem cells, ultimately resulting in proliferation of aberrantly differentiated cancer cells. Aldehyde dehydrogenase (ALDH), a detoxifying enzyme responsible for the oxidation of intracellular aldehydes, is a stem cell marker in several tissue types and tumors, including lung tumors. 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 NNK. Using LC-NSI-HRMS/MS-PRM, O6-methyl-G, 7-POB-G, and O2-POB-dT were positively identified in ALDH-positive lung 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.

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

246th National Meeting (2013)

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