This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Zhang, X Search for Related Content PubMed PubMed Citation Articles by Zhang, X Social Bookmarking                         What's this?

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

Bio-tech Engineering College, Jimei University, Xiamen 361021 Fujian, China xczhang{at}jmu.edu.cn

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.

Key Words: aberrant crypt foci • acrylamide • cancer • corn oil • mitochondria

Toxicology and Industrial Health, Vol. 25, No. 2, 101-109 (2009)
DOI: 10.1177/0748233709102948


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?