Colorectal cancer (CRC) is the third most common neoplasia in the United States. About 6% of individuals in the U.S. will develop invasive CRC during their lifetime. Although there is little difference in incidence between sub-populations in the U.S., world-wide the CRC incidence varies some ten-fold. This wide variation in colorectal cancer within different populations suggests that this cancer may be largely avoidable if causative and preventative factors are discovered. While there is a background of individual genetic susceptibility, an understanding of the complex influence of diet on CRC may improve the efforts in chemoprevention. There is strong epidemiological evidence for the benefits of fruit, vegetables and fiber in CRC prevention, with much supportive data from animal studies. However, there are numerous chemical compounds thought to be candidates for chemoprevention and many have multiple effects. This project utilizes the HT29 human colon cancer cell line to investigate the role of individual dietary factors in stimulating enhanced expression of the detoxification enzymes glutathione S-transferase and NAD(P)H: quinone reductase. Studies will be aimed at determining the influence of intracellular redox potential on these protective mechanisms. Although there are numerous studies suggesting that enzyme induction is influenced by redox potential, there are few studies designed to characterize this influence. This project will measure changed in intracellular concentrations of reduced and oxidized forms of glutathione (GSH), in response to dietary chemicals. GSH functions in a intracellular redox buffer, as well as serving a protective role against oxidative stress and carcinogenic electrophiles. The overall hypothesis of this study is that the protective mechanism of detoxification enzyme induction is responsive to measurable changes in cellular redox status. These findings will be applied to investigating the effects of redox potential of specific chemoprotection against the formation of a model carcinogen, benzo(a)pyrene.
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