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p53 mutations and aflatoxin B 1 exposure in hepatocellular carcinoma patients from thailand

1993; Wiley; Volume: 53; Issue: 1 Linguagem: Inglês

10.1002/ijc.2910530111

1097-0215

Monica Hollstein, Christopher P. Wild, Françoise Bleicher, Sopa Chutimataewin, Curtis C. Harris, Andpetcharin Srivatanakul, Ruggero Montesano,

DNA Repair Mechanisms

Abstract The prevalence and type of mutations in the p53 tumoursuppressor gene have been determined in 15 hepatocellular carcinomas (HCC) originating from Thailand. Direct sequencing of exons 5‐8 revealed 2 mutations, an AGG to AGT (Arg → Ser) transversion at codon 249, and an ATC → AAC (lle → Asn) transversion at codon 254. Samples from the Thai patients were analyzed for the presence of aflatoxin‐liver DNA and aflatoxinserum albumin adducts, and all but one were found negative. All the patients were genotyped for glutathione‐S‐transferase (GST) μ, an enzyme possibly involved in the detoxification of AFB 1 , and 12 out of 15 had the null genotype. In general, the level of aflatoxin‐albumin adducts in sera and the prevalence of p53 mutation at codon 249 in HCC were lower than in other areas at high risk of HCC, including southern China and parts of Africa.