The origin of colon cancer remains a problem. Epidemiological studies show that diets high in fat and low in cereal grain products are associated with an increased risk for the disease . However, they give no indication of the specific carcinogen or carcinogens responsible for the disease. This situation is likely to change. New toxicological methods make it possible to identify potential carcinogens in complex body fluids. This paper will consider our experience in the application of three such methods. In the application of each we have assumed that the carcinogenic factor originates in the colon contents and we have begun by searching for carcinogenic chemicals in the human feces. The three methods have led to the identification of three different groups of chemicals present in the feces that could be related to colon carcinogenesis. The work thus adds three new chemical hypotheses for the origin of colon cancer but does not define the cause of the disease.
The first method that we used was based on the assay developed by . This assay is based on the supposition that initiators for cancer are mutagens, and it detects as active chemicals those that induce back mutations in tester strains of Salmonella. Many fecal extracts were tested with the tester strains TA-98, TA-100, and TA-102 with and without the cytochrome P-450 activating system. The details of the extraction, testing, and eventual purification and identification have been published in detail elsewhere .
The mutagenic activity in the Ames assay was found in the extracts of the feces of approximately one-third of individuals on Western diets. The chromatographic purification of these extracts gave rise to fractions that were highly mutagenic. The compounds responsible were sensitive to light, oxygen, and acid, but their structure was finally identified as glycerol ethers linked to long-chain unsaturated alcohols . They were referred to as "fecapentaenes" because these compounds all possessed five conjugated double bonds, which explained their ability to form carbocations and thus, presumably, to act as mutagens .