Bressac B, Kew M, Wands J, Ozturk M
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Nature. 1991 Apr 4;350(6317):429-31. doi: 10.1038/350429a0.
Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen.
肝细胞癌（HCC）在撒哈拉以南非洲和东亚地区是一种常见癌症。乙型肝炎病毒和黄曲霉毒素是HCC的风险因素，但人类肝细胞癌发生的分子机制在很大程度上尚不清楚。肿瘤抑制基因p53的结构和表达异常在HCC细胞系中很常见，并且在中国和日本的HCC中已发现17号染色体短臂的等位基因缺失。在此，我们报告了在来自非洲南部的50%原发性HCC中发现的17号染色体短臂等位基因缺失和p53基因突变。检测到的5个突变中有4个是G→T替换，集中在密码子249处。这种突变特异性可能反映了对特定致癌物的暴露，一个候选物是黄曲霉毒素B1（参考文献7），它是非洲的一种食物污染物，既是一种诱导G到T替换的诱变剂，也是一种肝脏特异性致癌物。
