p53 gene mutations and abnormal retinoblastoma protein in radiation-induced human sarcomas.
p53 gene mutations and abnormal retinoblastoma protein in radiation-induced human sarcomas.
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发表时间：
1991-12
期刊：
影响因子：
11.2
通讯作者：
D. Brachman;D. Hallahan;M. Beckett;D. Yandell;R. Weichselbaum
中科院分区：
文献类型：
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作者：
D. Brachman;D. Hallahan;M. Beckett;D. Yandell;R. Weichselbaum
治疗性辐射的潜在致癌作用已被认识多年。第二种恶性肿瘤，通常是肉瘤，已知在最初的辐射照射几年后在辐射场内或辐射场边缘出现。我们分析了来自7个辐射诱导肿瘤的肿瘤细胞在DNA序列和/或蛋白质水平上的肿瘤抑制基因p53和视网膜母细胞瘤的异常。通过外显子特异性聚合酶链反应扩增和外显子5-8的单链构象多态性分析检测P53突变，然后对表现出变异模式的肿瘤进行直接基因组测序。在研究的6个肉瘤中，有3个p53基因异常。Western免疫印迹法进行视网膜母细胞瘤基因分析；视网膜母细胞瘤蛋白在7个肿瘤中有3个磷酸化不足，在另一个肿瘤中缺失。总的来说，7个辐射诱发的人类肿瘤中有6个具有一个或两个抑制基因的异常。电离辐射使肿瘤抑制基因失活可能导致辐射致癌。
The potentially carcinogenic effect of therapeutic irradiation has been recognized for many years. Second malignancies, usually sarcomas, are known to arise within or at the edge of radiation fields after a period of several years after the initial radiation exposure. We analyzed tumor cells derived from seven radiation-induced tumors for abnormalities in tumor suppressor genes p53 and retinoblastoma at the DNA sequence and/or protein level. p53 mutations were detected by exon-specific polymerase chain reaction amplification and single-strand conformation polymorphism analysis of exons 5-8 followed by direct genomic sequencing of those tumors exhibiting a variant pattern. The p53 gene was abnormal in three of six sarcomas studied. Retinoblastoma gene analysis was performed by Western immunoblot; retinoblastoma protein was under-phosphorylated in three of seven tumors and absent in one other. In all, six of seven radiation-induced human tumors have abnormalities of one or both suppressor genes. Inactivation of tumor suppressor genes by ionizing radiation may contribute to radiation carcinogenesis.