Research Interests: Nutritional Factors in Cancer: Food Mutagens and Chemoprevention/DNA Damage and Repair/Mechanisms of Mammalian Aging. Our laboratory studies dietary mutagens and breast cancer. In the United States, breast cancer is the most common cancer affecting women. Despite its high prevalence and enormous health impact, the causes of breast cancer are not well understood. The question of diet and breast cancer has attracted public attention because evidence is growing that diet may be contributing to the incidence of breast cancer in our country. In fact, it has been estimated that more than half of all breast cancers in the United States might be related to diet. Therefore, we would like to learn more about foods that pose a risk for breast cancer as well as foods that might protect against cancer. One source of dietary carcinogens that might influence the incidence of human breast cancer is called cooked meat mutagens because they are formed through heating protein-rich foods, such as meats and fish. The chemical name for cooked meat mutagens is heterocyclic amines. Although other chemicals can induce breast cancer in experimental animals, heterocyclic amines are the only mammary carcinogen known to be present in everyday human diets. To damage genes, cause mutations, and initiate cancer, the compounds formed by cooking meat require metabolic activation, which involves multiple enzyme steps that convert the original compound into a very reactive metabolite. The initiation of mammary cancer could be related to the ability of mammary gland cells to metabolize these compounds. Therefore, our lab is working to identify the enzymes responsible for metabolic activation of cooked meat mutagens, to characterize carcinogen processing in mammary gland cells, and to determine DNA repair of dietary mutagen damage in human breast cells. Changes in diet might someday alter breast cancer incidence, but chemical intervention offers an attractive approach for more immediate results. There are many natural products that have the ability to block gene damage or inhibit a different step in carcinogenesis. Anti-carcinogens, for example, are abundant in some fruits and vegetables, and several of these compounds have been shown to have preventive effects in the formation of rodent mammary tumors. We plan to study the ability of dietary anti-carcinogens to block gene damage and unregulated mammary cell growth induced by cooked meat mutagens. An understanding of the relationships between breast cancer and diet could lead to strategies to control breast cancer and therefore provide practical ways for primary prevention. This laboratory also has long-term interests in mechanisms of aging and DNA damage/repair. Representative Publications: Dubuisson JG and Gaubatz JW. Bioactivation of the food-derived mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to DNA binding species by human mammary gland enzymes, Nutrition, 1998; 14:683-686. Gaubatz JW. DNA base modification in aging, In: The Role of DNA Damage and Repair in Cell Aging, Gilchrest, B.A. and Bohr, W. (eds.) JAI Press, Inc., Stamford CT, in press (1999). Gaubatz JW. Heart damage associated with cooked meat mutagens, Journal of Nutritional Biochemistry, 1997; 8/9:490-496. Gaubatz JW and Tan BH. Introduction, distribution, and removal of 7-methylguanine in different liver chromatin fractions of young and old mice, Mutation Research, 1997; 375:25-35. Gaubatz JW. Cooked food mutagens and breast cancer, Nutrition, 1996; 12:449-450. Gaubatz JW. Genomic instability during aging of postmitotic mammalian cells, In: Molecular Basis of Aging, Macieira-Coelho, A., Ed., CRC Press (1995) pp. 71-136.
 
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