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DNA DAMAGES ARE VERY FREQUENT AND AN IMPORTANT CAUSE OF CANCER An average of more than 60000 endogenous DNA damages occur per cell per day in humans (Table ?(Table2).2). These are largely caused by hydrolytic reactions, interactions with reactive metabolites such as lipid peroxidation products, endogenous alkylating agents and reactive carbonyl species, and exposure to reactive oxygen molecules[28]. Table 2 Endogenous DNA damages/cell/day for humans However, buy LY294002 more important still in causing cancer, are DNA damages caused by exogenous agents. Doll et al[29] compared cancer rates for 37 specific cancers in the United States to rates for these cancers in countries where there is low incidence for these cancers. The populations for comparison included Norwegians, Nigerians, Japanese, British and Israeli Jews. They concluded that 75%-80% of the cases of cancer in the United States were likely avoidable. They indicated that the avoidable sources of cancer included tobacco, alcohol, diet (especially meat and fat), food additives, occupational exposures (including aromatic amines, benzene, heavy metals, vinyl chloride), pollution, industrial products, medicines and medical procedures, UV light from the sun, exposure to medical X-rays, and infection. Many of these sources of cancer are DNA damaging agents. One example of diet-related DNA damaging agents likely important in human GI cancer are bile acids. Bernstein et al[30] summarized 14 published reports showing that the secondary bile acids deoxycholic find more acid and lithocholic acid, formed by bacterial action in the colon, cause DNA damage. Bile acids are increased in the colon after the gall bladder releases bile acids into the digestive tract in response to consumption of fatty foods to aid in their digestion. Bile acids in the colon were doubled in the colonic contents of humans in the United States S6 Kinase who were on typical diets and then were experimentally fed a high fat diet[31]. Cancer rate comparisons can be made between two similar populations, one with low levels and one with high levels of colonic bile acids. For instance, deoxycholic acid (DOC) in the feces of Native Africans in South Africa is present at 7.30 nmol/g wet weight stool while for African Americans DOC is present at 37.51 nmol/g wet weight stool, a 5.14 fold higher concentration[32]. Native Africans in South Africa have a colon cancer rate of