UV AND SKIN-CANCER - SPECIFIC P53 GENE MUTATION IN NORMAL SKIN AS A BIOLOGICALLY RELEVANT EXPOSURE MEASUREMENT
UV AND SKIN-CANCER - SPECIFIC P53 GENE MUTATION IN NORMAL SKIN AS A BIOLOGICALLY RELEVANT EXPOSURE MEASUREMENT
复制标题
DOI：
10.1073/pnas.91.1.360
复制
发表时间：
1994-01-04
影响因子：
11.1
通讯作者：
YAMASAKI, H
中科院分区：
文献类型：
--
作者：
NAKAZAWA, H;ENGLISH, D;YAMASAKI, H
许多人类皮肤肿瘤含有突变的p53基因，这可能是紫外线照射造成的。为了研究紫外线照射与p53基因突变之间的联系，我们开发了两种方法来检测紫外线照射下正常皮肤中假定的紫外线特异性p53基因突变。这些方法是基于突变的等位基因特异性PCRS和连接酶链式反应，并设计用10杯DNA样本来检测密码子245和247/248上的CC到TT突变。这些特定的p53基因突变已经在皮肤肿瘤中得到了报道。只有紫外线照射后，培养的人皮肤细胞中才能检测到p53基因的CC到TT突变，且突变频率随着紫外线剂量的增加而增加。在澳大利亚皮肤癌患者日光照射部位的23例正常皮肤样本中，有17例(74%)存在P53基因245和247/248密码子之一或两个密码子的CC到TT突变，而来自非日光照射部位的20例正常皮肤样本中只有1例(5%)含有该突变。在居住在法国的志愿者身上，来自非日照或间歇性曝晒部位的15份正常皮肤活组织检查中没有一份携带这种突变。我们的结果表明，与人类皮肤癌相关的特定p53基因突变在正常皮肤中是由太阳紫外线辐射诱导的。这些突变的测量可能是有用的，作为人体紫外线暴露的生物学相关测量，以及作为皮肤癌风险的可能预测因子。
Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 mug of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer.