ABSENCE OF P53 MUTATIONS IN RAT COLON TUMORS INDUCED BY MINO-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 (H CAs), 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-pheny limidazo[4,5-b]pyridine (PhIP), and examined for p53 mutations. Seven carcinomas induced by Glu-P 1, and nine carcinomas and two adenomas in duced by IQ were examined by cDNA-polymerase chain reaction-single str and conformation polymorphism (PCR-SSCP) analysis from codon 103 to 39 1 of p53, which encompasses the conserved regions II to IV. Nine carci nomas induced by PhIP were examined by genomic PCR-SSCP analysis of ex ons 5 to 7 (from codon 124 to 304), which encompasses the 3' half of t he conserved region II and all the conserved regions III-V. No band sh ifts were found in any of these tumors under at least two conditions o f SSCP analysis. Our previous study had shown a Ki-ras mutation in onl y one Glu-P-1-induced adenocarcinoma among the same 27 colon tumors, a nd no other mutation of ras family genes had been found. HCA induced r at colon tumors appear to represent a group of human colon tumors in w hich neither Ki-ms nor p53 is involved.