CARCINOGENIC FACTORS IN FOOD WITH RELEVANCE TO COLON-CANCER DEVELOPMENT

The diet contains various mutagens and carcinogens that can be classified into three groups: naturally occurring chemicals, synthetic compounds and compounds produced by cooking. The first group includes mycotoxins and plant alkaloids while the second is exemplified by food additives and pesticides. The third includes polycyclic aromatic hydrocarbons and heterocyclic amines (HCAs). HCAs are mutagenic to microbes and eukaryotes and their precursors are creatine or creatinine, sugars, and amino acids in meat and fish. Among 10 HCAs so far examined for carcinogenicity in rodents, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-1-methyl-6-phenylinidazo[4,5-b]pyridine (PhIP) induced colon cancer in rats. PhIP is an especially interesting compound inducing colon tumors specifically in male F344 rats and only very rarely in females, which develop mammary carcinomas at high frequency instead. Since induced DNA adduct levels, determined by the 32 P-postlabeling method, were found to be almost the same in male and female F344 rats adduct formation in itself is not directly responsible for carcinogenesis. We established, however, that PhIP causes increased cell proliferation in colon mucosa but not in the non-target liver or kidney of male rats. Induction of cell proliferation is therefore possibly an additional important factor determining carcinogenic organ specificity. In terms of molecular alteration ras family gene mutations are very rare and no mutations are evident in the p53 gene in colon tumors induced by HCAs. Their development due to HCAs can thus be considered an appropriate experimental model for human colon tumors in which ras or p53 gene activation is not involved. Since HCAs are genotoxic compounds, a causal role in some stage of human colon carcinogenesis is plausible. Exposure to HCAs should accordingly be avoided as far as possible.