Jung M, Notario V, Dritschilo A
Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC 20007.
Cancer Res. 1992 Nov 15;52(22):6390-3.
Five of six human squamous cell carcinoma (SCC) cell lines characterized as radiation sensitive (SQ-38, SCC-9, SQ-9G) or radiation resistant (SQ-20B, SCC-35, JSQ-3) exhibited alterations of the p53 gene. The point mutations and a deletion were detected by using single-stranded conformational polymorphism analysis and polymerase chain reaction-direct sequencing. Interestingly, three of three radiation-sensitive and two of three radiation-resistant cell lines revealed mutations in the p53 gene. Point mutations were located in exons 4, 6, and 8 (at codons 72 and 298 in JSQ-3; 273 in SCC-35; 196 in SQ-38), and deletions consisted of 32 base pairs between codons 274 and 285 in SCC-9 and 1 base pair at codon 271 in SQ-9G. Three mutations resulted in substitutions for an arginine residue. Immunocytochemical analysis confirmed p53 protein overexpression in SCC-35 cells which contained a missense mutation at codon 273. In contrast to previous studies which linked alterations in ras, myc, and raf expression with radiation resistance, this study indicates that mutations in the tumor suppressor gene, p53, do not directly correlate with such resistance.
六种人鳞状细胞癌（SCC）细胞系中，有五种被鉴定为辐射敏感型（SQ - 38、SCC - 9、SQ - 9G）或辐射抗性型（SQ - 20B、SCC - 35、JSQ - 3），这些细胞系均表现出p53基因的改变。通过单链构象多态性分析和聚合酶链反应直接测序检测到了点突变和一个缺失突变。有趣的是，三种辐射敏感型细胞系中的三种以及三种辐射抗性型细胞系中的两种都发现了p53基因的突变。点突变位于外显子4、6和8（JSQ - 3中的密码子72和298；SCC - 35中的273；SQ - 38中的196），缺失突变包括SCC - 9中密码子274和285之间的32个碱基对以及SQ - 9G中密码子271处的1个碱基对。三种突变导致精氨酸残基被替代。免疫细胞化学分析证实，在密码子273处存在错义突变的SCC - 35细胞中p53蛋白过度表达。与之前将ras、myc和raf表达改变与辐射抗性联系起来的研究不同，本研究表明肿瘤抑制基因p53中的突变与这种抗性没有直接关联。
