GEOGRAPHIC-VARIATION OF P53 MUTATIONAL PROFILE IN NONMALIGNANT HUMAN LIVER

Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, C hina, contain an AGG to AGT mutation at codon 249 of the p53 tumor sup pressor gene, a mutation that is rarely seen in HCCs from Western coun tries. The population of Qidong is exposed to high levels of aflatoxin B-1 (AFB(1)), a fungal toxin that has been shown to induce the same m utation in cultured human HCC cells. To investigate the role of AFB(1) and of these p53 mutations in hepatocarcinogenesis, normal liver samp les from the United States, Thailand, and Qidong (where AFB(1) exposur es are negligible, low, and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paral leled the level of AFB(1) exposure, which supports the hypothesis that this toxin has a causative-and probably early-role in hepatocarcinoge nesis.