RARE FREQUENCY OF ACTIVATION OF THE KI-RAS GENE IN RAT COLON TUMORS INDUCED BY HETEROCYCLIC AMINES - POSSIBLE ALTERNATIVE MECHANISMS OF HUMAN COLON CARCINOGENESIS

Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility o f involvement of ras gene activation in colon carcinogenesis in rats a s in humans. We examined mutations at codons 12, 13, and 61 of the Ki- ras, Ha-ras, and N-ras genes by polymerase chain reaction-direct seque ncing in seven colon tumors in F344 rats induced by 2-amino-6-methyldi pyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-meth ylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1 -methyl-6-phe nylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G --> T at the seco nd position in codon 12) was found in one Glu-P-1-induced colon adenoc arcinoma. None of the other 26 tumors had mutations in any of these th ree ras family genes. These results indicate that in rats, colon carci nogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimen tal system using carcinogens to which humans are exposed is a good mod el for studying alterations of other genes in human colon tumors in wh ich no Ki-ras alterations are observed. (C) 1993 Wiley-Liss, Inc.