Morgan W F, Day J P, Kaplan M I, McGhee E M, Limoli C L
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, 94143-0750, USA.
Radiat Res. 1996 Sep;146(3):247-58.
Genomic instability is characterized by the increased rate of acquisition of alterations in the mammalian genome. These changes encompass a diverse set of biological end points including karyotypic abnormalities, gene mutation and amplification, cellular transformation, clonal heterogeneity and delayed reproductive cell death. The loss of stability of the genome is becoming accepted as one of the most important aspects of carcinogenesis, and the numerous genetic changes associated with the cancer cell implicate genomic stability as contributing to the neoplastic phenotype. Multiple metabolic pathways govern the accurate duplication and distribution of DNA to progeny cells; other pathways maintain the integrity of the information encoded by DNA and regulate the expression of genes during growth and development. For each of these functions, there is a normal baseline frequency at which errors occur, leading to spontaneous mutations and other genomic anomalies. This review summarizes the current status of knowledge about radiation-induced genomic instability. Those events and processes likely to be involved in the initiation and perpetuation of the unstable phenotype, the potential role of epigenetic factors in influencing the onset of genomic instability, and the delayed effects of cellular exposure to ionizing radiation are discussed.
基因组不稳定的特征是哺乳动物基因组中改变的获得率增加。这些变化包括一系列不同的生物学终点，包括核型异常、基因突变和扩增、细胞转化、克隆异质性以及延迟的生殖细胞死亡。基因组稳定性的丧失已被公认为是致癌作用最重要的方面之一，与癌细胞相关的众多基因变化表明基因组稳定性促成了肿瘤表型。多种代谢途径控制着DNA准确复制并分配给子代细胞；其他途径维持DNA编码信息的完整性，并在生长和发育过程中调节基因表达。对于这些功能中的每一项，都存在一个正常的基线错误发生频率，导致自发突变和其他基因组异常。本综述总结了关于辐射诱导基因组不稳定的当前知识状况。讨论了那些可能参与不稳定表型起始和持续的事件和过程、表观遗传因素在影响基因组不稳定发生中的潜在作用以及细胞暴露于电离辐射的延迟效应。
