Smith Leslie E, Nagar Shruti, Kim Grace J, Morgan William F
Radiation Oncology Research Laboratory, University of Maryland, 655 W. Baltimore Street, Baltimore, MD 21201-1559, USA.
Health Phys. 2003 Jul;85(1):23-9. doi: 10.1097/00004032-200307000-00006.
Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.
基因组不稳定性是一个用于描述一种现象的术语，该现象导致将正常细胞的稳定基因组转变为具有肿瘤特征的不稳定基因组所需的多种变化的积累。最近，关于基因组不稳定性在人类癌症中的重要性及其在致癌过程中的发生时间存在相当多的争论。辐射能够在哺乳动物细胞中诱导基因组不稳定性，并且这种不稳定性被认为是辐射致癌的驱动力。基因组不稳定性的特征是大量不同的终点，包括大规模染色体重排和畸变、遗传物质扩增、非整倍体、微核形成、微卫星不稳定性和基因突变。辐射诱导基因组不稳定性的能力在很大程度上取决于辐射质量或传能线密度（LET）以及剂量。低LET似乎存在低剂量阈值效应，超过该阈值不会诱导额外的基因组不稳定性。高LET和低LET辐射的低剂量都能够诱导这种现象。本报告回顾了有关高LET和低LET辐射的剂量率效应及其通过染色体畸变、延迟致死突变、微核和凋亡检测诱导基因组不稳定性能力的数据。
