p53 gene mutation in hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline in nonhuman primates.
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several heterocyclic amines formed during the cooking of proteinaceous foods. IQ is a potent carcinogen in rodent bioassays and causes a high incidence of hepatocellular carcinomas in nonhuman primates. We examined 20 hepatocellular carcinomas (HCCs) from nonhuman primates for mutations of the p53 gene using polymerase chain reaction-single strand conformational polymorphism analysis. Mutations in the p53 gene were detected in 4 of 20 HCCs (20%) with 3 showing G-to-T transversions and one a G-to-A transition. Three of these mutations were observed in codons 175 and 248 that are known mutational hot spots in human cancers. These data indicate that part of the IQ-induced HCCs in nonhuman primates may involve inactivation of the p53 gene and suggest that IQ and possibly other heterocyclic amines may participate in human carcinogenesis by a similar mechanism.
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Y
Y
Fujimoto
L L
LL
Hampton
E G
EG
Snyderwine
M
M
Nagao
T
T
Sugimura
R H
RH
Adamson
S S
SS
Thorgeirsson
D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics*; D016158:Genes, p53; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D009153:Mutagens; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011804:Quinolines / Q000494:pharmacology*
D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline