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• W4309506721 startingPage "79" @default.
• W4309506721 abstract "Colon cancer incidence is associated with a high-fat diet. Such a diet is linked to elevated levels of bile acids in the gastrointestinal system and the circulation. Secondary bile acids are produced by microorganisms present at high concentrations in the colon. Recent prospective studies and a retrospective study in humans associate high circulating blood levels of secondary bile acids with increased risk of colon cancer. Feeding mice a diet containing a secondary bile acid, so their feces have the bile acid at a level comparable to that in the feces of humans on a high-fat diet, also causes colon cancer in the mice. Studies using human cells grown in culture illuminate some mechanisms by which bile acids cause cancer. In human cells, bile acids cause oxidative stress leading to oxidative DNA damage. Increased DNA damage increases the occurrence of mutations and epimutations, some of which provide a cellular growth advantage such as apoptosis resistance. Cells with such mutations/epimutations increase by natural selection. Apoptosis, or programmed cell death, is a beneficial process that eliminates cells with unrepaired DNA damage, whereas apoptosis-resistant cells are able to survive DNA damage using inaccurate repair processes. This results in apoptosis-resistant cells having more frequent mutations/epimutations, some of which are carcinogenic. The experiments on cultured human cells have provided a basis for understanding at the molecular level the human studies that recently reported an association of bile acids with colon cancer, and the mouse studies showing directly that bile acids cause colon cancer. Similar, but more limited, findings of an association of dietary bile acids with other cancers of the gastrointestinal system suggest that understanding the role of bile acids in colon carcinogenesis may contribute to understanding carcinogenesis in other organs." @default.
• W4309506721 created "2022-11-28" @default.
• W4309506721 creator A5020458397 @default.
• W4309506721 creator A5062522223 @default.
• W4309506721 date "2022-11-19" @default.
• W4309506721 modified "2023-09-25" @default.
• W4309506721 title "Bile acids as carcinogens in the colon and at other sites in the gastrointestinal system" @default.
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