Kronenberg A
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Int J Radiat Biol. 1994 Nov;66(5):603-9. doi: 10.1080/09553009414551691.
Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.
对电离辐射暴露的可遗传体细胞效应进行定量评估，一直依赖于这样一种假设：辐射诱导的损伤在首次辐射后有丝分裂之前已在DNA中“固定”。损伤转化被认为发生在第一轮DNA复制期间，或者是损伤的易错酶处理的结果。评估各种辐射诱导终点（细胞死亡、特定基因座突变、肿瘤转化和染色体畸变）的标准实验方案，在单一时间点评估这些不同的终点。与上述方法不同，一些研究专门评估了辐射效应随暴露后时间的变化。已有证据支持辐射暴露会导致基因组持续不稳定这一假说。这种不稳定性表现为致死性突变的延迟表达、非致死性可遗传改变积累速率的加快以及克隆内染色体异质性的逐渐增加。辐射诱导基因组不稳定的遗传控制和生化机制尚未阐明。目的是整合已积累的证据，这些证据表明辐射暴露对哺乳动物基因组的稳定性有持续影响。
