CARCINOGENIC FACTORS IN FOOD WITH RELEVANCE TO COLON-CANCER DEVELOPMENT

The diet contains various mutagens and carcinogens that can be classif ied into three groups: naturally occurring chemicals, synthetic compou nds and compounds produced by cooking. The first group includes mycoto xins and plant alkaloids while the second is exemplified by food addit ives and pesticides. The third includes polycyclic aromatic hydrocarbo ns and heterocyclic amines (HCAs). HCAs are mutagenic to microbes and eukaryotes and their precursors are creatine or creatinine, sugars, an d amino acids in meat and fish. Among 10 HCAs so far examined for carc inogenicity in rodents, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazo le (Glu-P-1), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-ami no-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]pyrid ine (PhIP) induced colon cancer in rats. PhIP is an especially interes ting 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 an d female F344 rats adduct formation in itself is not directly responsi ble for carcinogenesis. We established, however, that PhIP causes incr eased cell proliferation in colon mucosa but not in the non-target liv er or kidney of male rats. Induction of cell proliferation is therefor e possibly an additional important factor determining carcinogenic org an specificity. In terms of molecular alteration ras family gene mutat ions are very rare and no mutations are evident in the p53 gene in col on tumors induced by HCAs. Their development due to HCAs can thus be c onsidered an appropriate experimental model for human colon tumors in which ras or p53 gene activation is not involved. Since HCAs are genot oxic compounds, a causal role in some stage of human colon carcinogene sis is plausible. Exposure to HCAs should accordingly be avoided as fa r as possible.