Sutherland B M, Bennett P V, Schenk H, Sidorkina O, Laval J, Trunk J, Monteleone D, Sutherland J
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Phys Med. 2001;17 Suppl 1:202-4.
Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- ~20%, with the other clustered damages being at least 80%.
簇状DNA损伤——在此定义为在几个螺旋圈范围内存在两个或更多损伤（链断裂、氧化嘌呤、氧化嘧啶或无碱基位点）——被认为难以精确修复，因此是具有高度生物学意义的损伤。此外，对簇状损伤的修复尝试可能会产生双链断裂（DSB）。然而，直到最近，除了双链断裂外，尚无办法测量电离辐射诱导的簇状损伤。我们最近描述了一种测量各类簇状损伤（氧化嘌呤簇、氧化嘧啶簇、无碱基簇以及双链断裂）的方法。我们发现，电离辐射（γ射线和铁离子，1 GeV/amu）确实会在溶液中的基因组DNA以及人类细胞中诱导产生此类簇状损伤。这些研究还表明，每个损伤簇均源自一次辐射撞击（及其径迹），因此表明它们可由极低剂量的辐射诱导产生，即簇状损伤的诱导并不需要两次独立的撞击。此外，在所有复杂损伤中，双链断裂最多占约20%，而其他簇状损伤至少占80%。
