Aflatoxin B1-induced rat hepatic hyperplastic nodules do not exhibit a site-specific mutation within the p53 gene.
Aflatoxin B1-induced rat hepatic hyperplastic nodules do not exhibit a site-specific mutation within the p53 gene.
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发表时间：
1993
期刊：
影响因子：
11.2
通讯作者：
J. Hulla;Zhi-Ying Chen;D. Eaton
中科院分区：
文献类型：
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作者：
J. Hulla;Zhi-Ying Chen;D. Eaton
越来越多的证据表明，p53肿瘤抑制基因在人类肝细胞癌（HCC）的发展中起着重要作用。最引人注目的是人类基因密码子249的明显突变特异性。黄曲霉毒素B1 （AFB）是一种肝脏特异性致癌物，可导致G向T取代。在非洲和亚洲患者中，约50%的HCC肿瘤在密码子249处检测到这种翻转。在这些地理区域，黄曲霉毒素暴露和乙型肝炎病毒感染是HCC的危险因素。与人类数据相反，在afb诱导的非人类灵长类动物肿瘤中未检测到密码子249突变。我们分析了afb诱导的大鼠肿瘤前肝结节中人类基因密码子249对应位点的p53基因。在检查的组织中未检测到突变。我们的数据表明，至少在大鼠中，单独暴露于AFB可能不足以确定HCC中观察到的p53突变的特异性。
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 non-human 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.