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Aflatoxin B₁-induced Rat Hepatic Hyperplastic Nodules Do Not Exhibit a Site-specific Mutation within the p53 Gene¹

Molecular Biology Section, Pacific Northwest Laboratory, Richland, Washington 99352 [J. E. H.], and Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195 [Z. Y. C., D. L. E.]

The weight of accumulated evidence suggests a role for the p53 tumor suppressor gene in the development of human hepatocellular carcinoma (HCC). Most striking is an apparent mutational specificity at codon 249 of the human gene. Aflatoxin B₁ (AFB) is a liver-specific carcinogen which causes G to T substitutions. This transversion was detected at codon 249 in about 50% of the analyzed HCC tumors from African and Asian patients. In these geographic regions aflatoxin exposure and hepatitis B viral infection are risk factors for HCC. In contrast to the human data, no mutations at codon 249 were detected in AFB-induced tumors from nonhuman primates. We have analyzed the p53 gene at the site corresponding to codon 249 of the human gene in AFB-induced preneoplastic hepatic nodules from rats. No mutations were detected in the tissues examined. Our data suggest that, at least in the rat, AFB exposure alone may not be sufficient for the specificity of p53 mutations observed in HCC.

¹ This work is supported in part by USPHS Grant ES03933 (D. L. E., Z. Y. C.) and by the United States Department of Energy under Contract DE-AC06-76RLO 1830 (J. E. H.).

² To whom requests for reprints should be addressed.

Received 10/16/92. Accepted 11/11/92.

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