Changes in apoptosis rather than cell proliferation best explain the effect of fat and fiber on colon carcinogenesis.
Conference Paper
Overview
Additional Document Info
View All
Overview
abstract
Maintenance of a healthy colonie epithelium is a delicate balance between cell birth and death, which may be disrupted during the tumorigenic process. We determined the relative importance of cell proliferation and death (apoptosis) to colon tumorigenesis as a function of fat and fiber. Two hundred forty male Sprague Dawley rats received one of 2 fats (com oil or fish oil); 2 fibers (pectin or cellulose); plus or minus the carcinogen azoxymethane (AOM). Eighty rats were killed at week 18; 160 at week 35. hi vivo cell proliferation was measured immunohistochemically using incorporation of bromodeoxyuridine into DNA. Apoptosis was measured by immunoperoxidase detection of digoxigenin-labeled genomic DNA. The percentage of animals with adcnocarcinomas was: corn/cellulose 75.6%; corn/pectin 63.6%; fish/cellulose 60.6%; fish/pectin 54.5%. These results are not explained by the effect of fat or fiber on cell proliferation since neither diet component affected labeling index or prolifcrative zone at either week 18 or 35. In contrast, at week 18 there was a main effect of fat (p-0.026) and fiber (p-0.071) on the proportion of apoptotic cells in the crypt (fish/pectin 8.71%; fish/cellulose 7.13%; com/pectin 6.86%; corn/cellulose 6.19%). This same pattern of fisbxxxn, pectin>cellulose was also found at week 35, with a greater number of apoptotic cells/crypt produced by fish oil vs com oil (P=0.0023) and pectin vs cellulose (P=0.0014). The combined effect of fat and fiber waja two fold difference in numbers of apoptotic cells/crypt between fish/pectin (0.88) compared to corn/ cellulose (0.38). These results suggest that an increase in apoptosis, rather than a decrease in proliferation, accounts for the protective effect offish oil and pectin against experimentally-induced colon tumorigenesis. Support- NIH CA59034 and CA61750.
