Huang Lei, Snyder Andrew R, Morgan William F
Graduate Program in Human Genetics, University of Maryland, 655 W. Baltimore St., Baltimore, MD 21201-1559, USA.
Oncogene. 2003 Sep 1;22(37):5848-54. doi: 10.1038/sj.onc.1206697.
Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.
辐射诱导的基因组不稳定性的特征是，在初始损伤后的多代受照细胞后代中，遗传改变的发生率增加，包括细胞遗传学重排、突变、基因扩增、转化和细胞死亡。染色体重排是辐射诱导的基因组不稳定性最具特征的终点，并且所描述的许多重排与人类癌症中发现的重排相似。染色体断裂综合征由染色体不稳定性定义，患有这些疾病的个体易患癌症。因此，作为一种表型的染色体不稳定性可能是导致癌症的某些变化的部分原因。在这里，我们试图将关于辐射诱导的染色体不稳定性的现有知识与关于染色体断裂综合征的新出现的分子信息联系起来。目的是了解遗传和表观遗传因素如何影响染色体不稳定性的发生以及染色体不稳定性在致癌作用中的作用。
