ABSENCE OF P53 MUTATIONS IN RAT COLON TUMORS INDUCED BY 2-AMINO-6-METHYLDIPYRIDO[1,2-ALPHA-3',2'-D]IMIDAZOLE, 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE, OR 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE

Colon tumors were induced in F344 rats by three heterocyclic amines (HCAs), 2-amino-6-methyl-dipyrido[1,2-a:3', 2'-d]imidazole (Glu-P-1), 2-amino 3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and examined for p53 mutations. Seven carcinomas induced by Glu-P 1, and nine carcinomas and two adenomas induced by IQ were examined by cDNA-polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis from codon 103 to 391 of p53, which encompasses the conserved regions II to IV. Nine carcinomas induced by PhIP were examined by genomic PCR-SSCP analysis of exons 5 to 7 (from codon 124 to 304), which encompasses the 3' half of the conserved region II and all the conserved regions III-V. No band shifts were found in any of these tumors under at least two conditions of SSCP analysis. Our previous study had shown a Ki-ras mutation in only one Glu-P-1-induced adenocarcinoma among the same 27 colon tumors, and no other mutation of ras family genes had been found. HCA induced rat colon tumors appear to represent a group of human colon tumors in which neither Ki-ms nor p53 is involved.