Absence of p53 Mutations in Rat Colon Tumors Induced by 2‐Amino‐6‐methyldipyrido[1,2‐<i>a</i>:3′, 2′‐<i>d</i>]imidazole, 2‐Amino‐3‐methylimidazo[4,5‐<i>f</i>]quinoline, or 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐<i>b</i>]pyridine

Abstract

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-ras nor p53 is involved.