GENETIC ALTERATIONS IN RAT COLON TUMORS INDUCED BY HETEROCYCLIC AMINES

BACKGROUND. In rat colon tumors induced by the cooked food mutagens 2- amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-met hylimidazo[4,5-f]quinoline (IQ), ras and p53 alterations are rarely de tected. To investigate the roles of the APC gene and microsatellite in stability (MI) in PhIP-induced colon carcinogenesis, mutations of the APC gene and alterations of microsatellites were examined. METHODS. Co mplementary DNA sequence of the rat APC gene were determined by polyme rase chain reaction (PCR) using primers based on the human APC sequenc e. PCR-single strand conformation polymorphism (SSCP) analysis was per formed using primers based on sequences of flanking introns and exon 1 5. Microsatellite alterations were also analyzed using 85 microsatelli te sequences dispersed through most of the rat chromosomes. RESULTS. F ive mutations In the APC gene were detected in four of eight PhIP-indu ced rat colon tumors. All five mutations involved deletion of a guanin e base in a 5'-GGGA-3' sequence. Only 2 of 13 IQ-induced colon tumors had mutations of the APC gene and these were base substitution mutatio ns. Seven of eight PhIP-induced colon tumors had microsatellite altera tions in at least one locus, whereas no alterations were observed in t he IQ-induced colon tumors. CONCLUSIONS. The specific 5'-GGGA-3' to 5' -GGA-3' mutation and MI demonstrated in this study are strong evidence of a mutational fingerprint of PhIP. (C) 1996 American Cancer Society .