Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens.
Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens.
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发表时间：
1991-11
期刊：
影响因子：
11.2
通讯作者：
A. Puisieux;Susan E. Lim;J. Groopman;M. Ozturk
中科院分区：
文献类型：
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作者：
A. Puisieux;Susan E. Lim;J. Groopman;M. Ozturk
在肺癌和肝癌中，p53 突变主要是 G:C 到 T:A 颠换。已知这种类型的突变是由苯并（a）芘和黄曲霉毒素 B1 诱导的，它们分别与肺癌和肝癌的病因有关。使用基于 DNA 聚合酶指纹分析的新型检测方法，我们鉴定了这些致癌物靶向的 p53 核苷酸。肺癌中经历 G:C 到 T:A 突变的 p53 基因的 14 个核苷酸残基中的 13 个是苯并 (a) 芘的靶标。同样，黄曲霉毒素 B1 在肝癌特异性突变热点处形成加合物。相同的核苷酸（密码子 249 的第三个碱基）在肺癌中很少发生突变，但不是苯并（a）芘的目标。这些体外观察表明，在不同肿瘤中鉴定出的 p53 突变热点是专门针对病因学确定的环境致癌物选择的靶点。
In lung and liver cancers, p53 mutations are mostly G:C to T:A transversions. This type of mutation is known to be induced by benzo(a)pyrene and aflatoxin B1 which are associated with the etiology of lung and liver cancers, respectively. Using a novel assay based on DNA polymerase fingerprint analysis, we identified p53 nucleotides targeted by these carcinogens. Thirteen of 14 nucleotide residues of the p53 gene which underwent G:C to T:A mutations in lung cancers were targeted by benzo(a)pyrene. Similarly, aflatoxin B1 formed adducts at a mutational hotspot specific for liver cancer. The same nucleotide (third base of codon 249), which mutates rarely in lung cancers, was not a target for benzo(a)pyrene. These in vitro observations indicate that p53 mutational hotspots identified in different tumors are selected targets specifically for the etiologically defined environmental carcinogens.