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SANDMAN
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DNA and Protein Adducts as Biomarkers for Carcinogen Exposure and Metabolism

presented by

Gunnar Boysen
Director of Mass Spec., The University of North Carolina at Chapel Hill

March 09, 2006

The Scripps Research Institute, W.M. Keck Foundation Amphitheater


Background:


  • University of Kaiserslautern, B.S., 1994, Biology

  • University of Kaiserslautern, and German Cancer Research Center, Heidelberg, Germany M.S., 1996, Biology

  • University of Kaiserslautern and University of Minnesota Cancer Center, Minneapolis, MN, Ph.D., 2002, Chemistry

  • University of North Carolina Chapel Hill, NC, Ph.D., 2002-2005, Toxicology

Abstract:

DNA and protein adducts have been used as markers for exposure and internal uptakes since several decades mainly using 32P-postlabeling and ELISA. Expectations were high and often not achieved. However, recent advances in mass spectrometry have lead to highly specific and sensitive assays. This seminar will demonstrate the successful application of DNA adducts to study the effects of isothiocyanates (ITC) on tobacco carcinogen metabolism. Further data will be shown where hemoglobin adducts are applied to understand the spices differences in butadiene metabolism and carcinogenesis. Last, it will be shown that butadiene monoepoxide can bind to P450 2E1 at residues theoretically important for enzyme activity. Together these studies will demonstrate that analysis of DNA or protein adducts can provide important information regarding the mode of action of chemical carcinogens.

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