Clustered damages and total lesions induced in DNA by ionizing radiation: Oxidized bases and strand breaks
Clustered damages and total lesions induced in DNA by ionizing radiation: Oxidized bases and strand breaks
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DOI：
10.1021/bi9927989
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发表时间：
2000-07-11
期刊：
影响因子：
2.9
通讯作者：
Laval, J
中科院分区：
文献类型：
--
作者：
Sutherland, BM;Bennett, PV;Laval, J
电离辐射诱导孤立的DNA损伤和集群损伤-多个紧密间隔的损伤（链断裂，氧化嘌呤，氧化嘧啶，或几个螺旋圈内的脱碱基位点）。这种簇被认为是难以修复的，因此可能是致命的或致突变的病变。使用高度纯化的酶，切割DNA在特定类别的损害和电泳分析开发的定量分离和集群的损害在高分子长度的基因组DNA，我们确定了总病变和集群的损害，涉及两条链的相对频率，和组成和起源这样的集群。孤立与集群损伤的相对频率取决于病变的身份，分别由Fpg，Nth或Nfo蛋白识别的集群中的氧化嘌呤，嘧啶或脱碱基位点的相似性为15-18%，但双链断裂中的坦率单链断裂水平仅为约一半。氧化碱基簇和脱碱基位点簇构成约80%的复合损伤，而双链断裂仅占总数的20%。数据还表明，每个集群的结果从一个单一的辐射（轨迹）事件，因此集群将形成在低以及高辐射剂量。
Ionizing radiation induces both isolated DNA lesions and clustered damages-multiple closely spaced lesions (strand breaks, oxidized purines, oxidized pyrimidines, or abasic sites within a few helical turns). Such clusters are postulated to be difficult to repair and thus potentially lethal or mutagenic lesions. Using highly purified enzymes that cleave DNA at specific classes of damage and electrophoretic assays developed for quantifying isolated and clustered damages in high molecular length genomic DNAs, we determined the relative frequencies of total lesions and of clustered damages involving both strands, and the composition and origin of such clusters. The relative frequency of isolated vs clustered damages depends on the identity of the lesion, with similar to 15-18% of oxidized purines, pyrimidines, or abasic sites in clusters recognized by Fpg, Nth, or Nfo proteins, respectively, but only about half that level of frank single strand breaks in double strand breaks. Oxidized base clusters and abasic site clusters constitute about 80% of complex damages, while double strand breaks comprise only similar to 20% of the total. The data also show that each cluster results from a single radiation (track) event, and thus clusters will be formed at low as well as high radiation doses.