Research Abstracts Online
January 2009 - March 2010
University of Minnesota Twin Cities
Academic Health Center
Masonic Cancer Center
PI: Stephen S. Hecht, Associate Fellow
Biochemistry, Biology, and Carcinogenicity of Tobacco-specific N-Nitrosamines
The tobacco-specific nitrosamines N’-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are considered to be among the major causative agents for cancer induction by tobacco products. NNN and NNK are metabolically activated in mammalian systems by cytochrome P450 enzymes that convert them to forms that are chemically reactive. These reactive intermediates bind to DNA to form covalently bound products called DNA adducts that are absolutely critical in cancer induction.
The goal of this research is to determine the structures of these DNA adducts. NMR is the main method by which this structural analysis is performed. Chemically activated forms of NNN and NNK are allowed to react with calf thymus DNA. The DNA is them enzymatically hydrolyzed to deoxyribonucleosides. These are isolated and purified, then subjected to NMR analysis. The group uses MSI resources for acquisition and interpretation of these spectra, using specialized techniques. Once the structures of the DNA adducts are determined, methods of their quantitative analysis in tissues of laboratory animals or humans exposed to these carcinogens can be developed.
Silvia Balbo, Research Associate
Siyi Zhang, Graduate Student