NO INVOLVEMENT OF KI-RAS OR P53 GENE-MUTATIONS IN COLITIS-ASSOCIATED RAT COLON TUMORS INDUCED BY 1-HYDROXYANTHRAQUINONE AND METHYLAZOXYMETHANOL ACETATE

1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and met hylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show syn ergistic carcinogenicity in rat colon, and 1-HA induces ulcerative cha nges with simultaneous severe inflammation of the entire colon. In thi s study, mutations in Ki-ras (exons 1 and 2) and p53 (exons 4-7) were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Of 18 adenomas and 38 adenocarcinomas in duced in male F344 rats (52 tumors induced by 1-HA plus MAM acetate, t hree by 1-HA alone, and one by MAM acetate alone), no mutations in Ki- ras or p53 were detected under two conditions of PCR-SSCP analysis. Be cause human colon carcinomas from patients with ulcerative colitis hav e a very low incidence of Ki-ras mutation, this experimental system wo uld be a good animal model of human colon carcinomas with ulcerative c olitis and of human colon carcinomas without Ki-ras or p53 mutations. (C) 1995 Wiley-Liss, Inc.