GEOGRAPHIC-VARIATION OF P53 MUTATIONAL PROFILE IN NONMALIGNANT HUMAN LIVER
GEOGRAPHIC-VARIATION OF P53 MUTATIONAL PROFILE IN NONMALIGNANT HUMAN LIVER
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DOI：
10.1126/science.8191284
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发表时间：
1994-05-27
期刊：
影响因子：
56.9
通讯作者：
CERUTTI, P
中科院分区：
文献类型：
--
作者：
AGUILAR, F;HARRIS, CC;CERUTTI, P
在启东、中国等地的肝细胞癌中，58%存在p53抑癌基因第249位密码子的agg到agt突变，这种突变在西方国家的肝细胞癌中很少见。启东的人群暴露在高水平的黄曲霉毒素B-1(AFB(1))中，这是一种真菌毒素，已被证明在培养的人类肝癌细胞中会诱导同样的突变。为了研究AFB(1)和这些p53突变在肝癌发生中的作用，对来自美国、泰国和启东的正常肝脏样本(AFB(1)暴露分别可忽略、低和高)进行了p53突变检测。第249位密码子AGG到AGT突变的频率与AFB(1)的暴露水平平行，这支持了这种毒素在肝癌发生中具有致病作用--可能是早期作用--的假设。
Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. 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 mutation in cultured human HCC cells. To investigate the role of AFB(1) and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB(1) exposures are negligible, low, and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB(1) exposure, which supports the hypothesis that this toxin has a causative-and probably early-role in hepatocarcinogenesis.