Simultaneous exposure to dietary acrylamide and corn oil developed carcinogenesis through cell proliferation and inhibition of apoptosis by regulating p53 -mediated mitochondria-dependent signaling pathway
Restricted accessResearch articleFirst published online March, 2009
Simultaneous exposure to dietary acrylamide and corn oil developed carcinogenesis through cell proliferation and inhibition of apoptosis by regulating p53 -mediated mitochondria-dependent signaling pathway
To investigate whether simultaneous exposure to acrylamide (ACR) and long-term dietary corn oil induces colon cancer by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis in rats. Male Sprague-Dawley rats were given intraperitoneal injections of ACR at dose of 10 mg/kgbw and diets supplemented with 10% corn oil for 8 wks; and then rats were still fed with diets supplemented with 10% oil for other 48 wks. Colonic aberrant crypt foci (ACF) and tumors, including adenomas and carcinomas, were examined at 12, 24, 36, 48 week post ACR-exposure. Colonic apoptosis and cell proliferation, expression of Wild type (wt) p53, Bcl-2, Bax and caspase-3, were detected at 48 week post ACR-exposure. ACF was found at 12 week and colon cancer invasion was found at 48 week in ACR rats on long-term dietary corn oil. Apoptosis was decreased and cell proliferation was increased in colonic mucosa in ACR-treated rats on dietary corn oil compared to vehicle rats on basal diet (P < 0.05). In ACR rats on dietary corn oil, mitochondrial wt p53 was significantly inhibited through decreased mitochondrial localization of wt p53 and increased cytosolic p53, resulting in the up-regulation of Bcl-2 and the down-regulation of Bax in the mitochondria, also inhibition of the release of cytochrome-c from the mitochondria into the cytosol and protein level of caspase-3 (P < 0.05). Results suggest that simultaneous exposure to ACR and long-term dietary corn oil induces development of colon cancer partly by inhibiting the tumor suppressor gene p53-mediated mitochondria-dependent apoptosis.
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