Vamvakas S, Vock E H, Lutz W K
Department of Toxicology, University of Würzburg, Germany.
Crit Rev Toxicol. 1997 Mar;27(2):155-74. doi: 10.3109/10408449709021617.
DNA double-strand breaks are associated with various endogenous processes, such as transcription, recombination, replication, and with the process of active cell death, which aims to eliminate cells. In addition, DNA double-strand breaks can be induced by irradiation, exposure to chemicals, increased formation of reactive oxygen species, and, indirectly, during repair of other types of DNA damage or as a consequence of extranuclear lesions. In addition to the neutral filter elution of DNA, the recently introduced pulsed-field gel electrophoresis is capable of determining DNA double-strand breaks with higher accuracy and sensitivity and is expected to increase our knowledge on the frequency and the role of DNA breakage. Parallel determination of parameters for cytotoxicity is necessary to elucidate the causal primary lesion. Although the repair of DNA double-strand breaks is a complex task, cells are capable of repairing--with or without errors and up to a certain extent--and surviving this DNA lesion. Gene translocations, rearrangements, amplifications, and deletions arising during repair and misrepair of double-strand breaks may contribute to cell transformation and tumor development.
DNA双链断裂与多种内源性过程相关，如转录、重组、复制，以及旨在清除细胞的主动细胞死亡过程。此外，DNA双链断裂可由辐射、化学物质暴露、活性氧物种形成增加间接诱导，在修复其他类型的DNA损伤过程中或作为核外损伤的结果也可诱导产生。除了DNA的中性滤膜洗脱法，最近引入的脉冲场凝胶电泳能够更准确、灵敏地测定DNA双链断裂，有望增加我们对DNA断裂频率及其作用的认识。同时测定细胞毒性参数对于阐明因果原发性损伤是必要的。虽然DNA双链断裂的修复是一项复杂的任务，但细胞能够在有或无错误的情况下，在一定程度上修复这种DNA损伤并存活下来。双链断裂修复和错配修复过程中出现的基因易位、重排、扩增和缺失可能导致细胞转化和肿瘤发展。
