Tobacco smoking is one of the leading causes of oral cancer. Our laboratory had developed a mouse model of oral cancer induced by the environmental pollutant and tobacco smoke component DB[a,l]P. We hypothesized that the stereochemical course of DB[a,l]P metabolism, the conformations of the DNA adducts formed and their removal by DNA repair enzymes, all play critical roles in the induction of oral carcinogenesis. As an initial study to test our hypothesis, we have developed a LC-MS/MS method to detect and quantify DB[a,l]PDE-N6-dA  and DB[a,l]PDE-N2-dG adducts in oral tissues of mice treated with DB[a,l]P. We detected (-)-anti-cis- and (-)-anti-trans-DB[a,l]PDE-N6-dA, as well as, (-)-anti-cis- and (-)-anti-trans-DB[a,l]PDE-N2-dG adducts in oral tissues of mice treated with DB[a,l]P; the results indicate that dA adducts are significantly higher than dG adducts and that DB[a,l]P is predominantly metabolized to (-)-anti-DB[a,l]PDE.

Identification and quantification of DNA adducts in the oral tissues of mice treated with the environmental carcinogen dibenzo[<i>a,l</i>]pyrene (DB[<i>a,l</i>]P) by liquid chromatography-tandem mass spectrometry (LC-MS/MS)

244th National Meeting (2012)

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Identification and quantification of DNA adducts in the oral tissues of mice treated with the environmental carcinogen dibenzo[a,l]pyrene (DB[a,l]P) by liquid chromatography-tandem mass spectrometry (LC-MS/MS)