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DNA Adducts Arising from Tobacco-derived N-nitrosamines

Institution: University of California, Riverside
Investigator(s): Yinsheng Wang, Ph.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18XT-0073 Award: $250,000
Subject Area: General Biomedical Science
Award Type: Exploratory/Developmental Award

Initial Award Abstract
Cigarette smoking is the major risk factor for the development of lung cancer in developed countries. Tobacco and its smoke contain a large number of reactive chemicals, which can bind to human genetic material, DNA. In this study, we will focus on examining the biological consequences of the DNA modifications induced by two abundant tobacco-derived N-nitrosamines, which have been shown previously to be carcinogenic to laboratory animals and are considered carcinogenic to humans by the International Agency for Research on Cancer. In particular, we will ask whether the modified DNA blocks the replication of genomic DNA and whether it introduces mistakes during DNA copying process. The results from this study will offer important insights into the mechanisms of carcinogenesis of these abundant cigarette smoke components.

Quantification of N2-carboxymenthyl-2-deoxyguansine in calf-thymus DNA and cultured human kidney epithelial cells by capillary LC tandem mass spectrometry coupled with stable isotope-dilution method.
Periodical: Chemical Research in Toxicology Index Medicus:
Authors: Wang H, Cao H, Wang Y ART
Yr: 2010 Vol: Nbr: 23 Abs: Pg: 74-81

The roles o DNA polymerases k and i in the erro-free bypass of N2-carboxyalkyl-dG lesions in mammalian cells.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Yuan, B.; You, C.; Anderson, N.; Jiang, Y.; Moriya, M.; O'Connor, T.R. and Wang, Y. ART
Yr: 2011 Vol: 286 Nbr: Abs: Pg: 17503-17511