Absence of p53 mutations in rat colon tumors induced by 2-amino-6-methyldipyrido[1,2-a: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-ras nor p53 is involved.
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo.
H
H
Makino
T
T
Ushijima
H
H
Kakiuchi
M
M
Onda
N
N
Ito
T
T
Sugimura
M
M
Nagao
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics*; D011905:Genes, ras; D007093:Imidazoles; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011804:Quinolines; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D007093:Imidazoles; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine