This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lung cancer is the leading cause of cancer death in the U.S. Approximately 90% of lung cancer is caused by cigarette smoking. While the best way to prevent lung cancer is cessation of smoking, most smokers cannot stop. An alternate approach to decrease risk is the use of chemopreventive agents. In this proposal, we are attempting to develop methodology to evaluate the ability of chemopreventive agents to block DNA adduct formation in the lungs of smokers. DNA adduct formation is critical in the cancer induction process. Animal studies show that a chemopreventive agent - phenethyl isothiocyanate (PEITC) - can block DNA adduct formation by a tobacco-specific lung carcinogen NNK. We wish to extend this work to humans in Phase II trials of PEITC. In order to do this, we must be able to measure NNK DNA adducts in small amounts of DNA which can be obtained by bronchial lavage or from sputum. AMS is one method to accomplish this. In this proposal, we describe experiments toward the development of an AMS method to detect and quantify NNK-DNA adducts in small DNA samples using AMS. We will apply this methodology to DNA containing a known amount of the adducts, diluted with unmodified DNA to concentrations in the range which we expect in human samples. We will compare the adduct levels determined by the AMS method to the known amounts in this DNA. When the accuracy of the method has been determined in such experiments, we will then be ready to extend it to human samples.
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