a Department of Epigenetics and Molecular Carcinogenesis , The University of Texas MD Anderson Cancer Center , Smithville , TX , USA.
b Department of Pathology , The University of Mexico School of Medicine , Albuquerque , NM , USA.
Cell Cycle. 2017 Jun 18;16(12):1153-1163. doi: 10.1080/15384101.2017.1312234. Epub 2017 Jun 8.
Tissue culture and mouse model studies show that the presence of the arginine (R) or proline (P) coding single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 at codon 72 (p53 R72P) differentially affects the responses to genotoxic insult. Compared to the P variant, the R variant shows increased apoptosis in most cell cultures and mouse model tissues in response to genotoxins, and epidemiological studies suggest that the R variant may enhance cancer survival and reduce the risks of adverse reactions to genotoxic cancer treatment. As ionizing radiation (IR) treatment is often used in cancer therapy, we sought to test the physiological effects of IR in mouse models of the p53 R72P polymorphism. By performing blood counts, immunohistochemical (IHC) staining and survival studies in mouse populations rigorously controlled for strain background, sex and age, we discovered that p53 R72P polymorphism did not differentially affect the physiological response to IR. Our findings suggest that genotyping for this polymorphism to personalize IR therapy may have little clinical utility.
组织培养和小鼠模型研究表明,抑癌基因 p53 密码子 72 处的精氨酸(R)或脯氨酸(P)编码单核苷酸多态性(SNP)的存在(p53 R72P)会对基因毒性损伤的反应产生不同的影响。与 P 变体相比,R 变体在大多数细胞培养物和小鼠模型组织中对基因毒性物质的反应表现出增加的细胞凋亡,并且流行病学研究表明,R 变体可能增强癌症的存活率并降低对基因毒性癌症治疗的不良反应的风险。由于电离辐射(IR)治疗常用于癌症治疗,我们试图在 p53 R72P 多态性的小鼠模型中测试 IR 的生理效应。通过对严格控制品系背景、性别和年龄的小鼠群体进行血细胞计数、免疫组织化学(IHC)染色和生存研究,我们发现 p53 R72P 多态性不会对 IR 的生理反应产生差异影响。我们的研究结果表明,针对这种多态性进行基因分型以实现 IR 治疗的个体化可能没有多少临床实用性。