THE ROLE OF APOPTOSIS IN THE MODULATION OF COLON CARCINOGENESIS BY DIETARY-FAT AND BY THE ORGANOSELENIUM COMPOUND 1,4-PHENYLENEBIS(METHYLENE) SELENOCYANATE

Studies in laboratory animals have demonstrated that dietary supplemen ts of organoselenium, 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibit colon carcinogenesis. Diverse chemopreventive agents and clin ically used anticancer drugs have been shown to induce apoptosis in co lonic tumors, Inducing apoptosis is a key mechanism for the effectiven ess of some chemopreventive agents; however, failure of apoptosis is n ow believed to contribute to the development of human cancer, In this study, we determined the number of apoptotic bodies in the colon tumor s of rats fed a low-fat (LF) or a high-fat (HF) diet with or without p -XSC treatment, At 5 weeks of age, male F344 rats were divided into fo ur groups, which were then maintained on one of the following diets: L F, 5% corn oil; HF, 23.5% corn oil; and LF and HF supplemented with 20 ppm p-XSC, In addition, the LF or HF diet with p-XSC supplements was administered either during the initiation stage or postinitiation, At 7 weeks of age, all rats except those intended for vehicle (normal sal ine) treatment were given 15 mg/kg of body weight of azoxymethane once weekly for 2 weeks, The animals were sacrificed 38 weeks after carcin ogen treatment, and their colonic tumors were examined for appearance of apoptosis. The LF diet significantly increased the percentage of ap optosis as compared to the HF diet; the percentage of apoptosis in LF and HF diets were 12.4 and 2.9, The colon tumors that were present in the groups fed p-XSC together with a LF or a HF diet after carcinogen administration (postinitiation period) had a higher number of apoptoti c bodies than those that were present in the animals fed p-XSC before carcinogen treatment (initiation period), The extent of apoptosis was weak when p-XSC was given with a HF diet (4.4%) during the initiation phase, but it was highly significant when p-XSC was administered with LF diet (25.2%), Taken together, our data suggest that administration of LF diet supplemented with p-XSC increases apoptosis as compared to a HF diet alone.