p53 Gene Mutation in Hepatocellular Carcinoma Induced by 2‐Amino‐3‐methylimidazo[4,5‐f]quinoline in Nonhuman Primates

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Abstract
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 nonhnman 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.