Elkind M M
Cancer. 1985 Nov 15;56(10):2351-63. doi: 10.1002/1097-0142(19851115)56:10<2351::aid-cncr2820561002>3.0.co;2-h.
The evidence supporting a cause and effect relationship between DNA damage and cell killing is examined in the light of what is currently known about the organization and replication of genomic DNA in eukaryotic cells and the radio-energetics of DNA breakage. A large disparity is identified between characteristic doses for cell killing and for the production of DNA lesions (i.e., single- or double-strand breaks). In contrast, the sensitive phase of the inhibition of DNA synthesis has a dependence on dose quantitatively similar to that of cell killing. A model is developed in which single- and double-strand breaks are associated with the inhibition of replicon initiation, whereas only double-strand breaks are primarily responsible for strand elongation. Furthermore, the model points to the replisome and the region of replicated DNA just downstream from the fork as the locus of radiation action.
根据目前对真核细胞基因组DNA的组织和复制以及DNA断裂的放射能量学的了解，对支持DNA损伤与细胞杀伤之间因果关系的证据进行了研究。结果发现，细胞杀伤的特征剂量与DNA损伤（即单链或双链断裂）产生的特征剂量之间存在很大差异。相比之下，DNA合成抑制的敏感阶段对剂量的依赖性在数量上与细胞杀伤相似。我们建立了一个模型，其中单链和双链断裂与复制子起始的抑制相关，而只有双链断裂主要负责链的延伸。此外，该模型指出复制体和叉下游的复制DNA区域是辐射作用的位点。
