Xapsos M A, Pogozelski W K
Radiation Effects Branch, Naval Research Laboratory, Washington, D.C. 20375, USA.
Radiat Res. 1996 Dec;146(6):668-72.
Although double-strand breaks have long been recognized as an important type of DNA lesion, it is well established that this broad class of damage does not correlate well with indicators of the effectiveness of radiation at the cellular level. Assays of double-strand breaks do not distinguish the degree of complexity or clustering of singly damaged sites produced in a single energy deposition event, which is currently hypothesized to be key to understanding cellular end points. As a step toward this understanding, double-strand breaks that are formed proportionally to dose in plasmid DNA are analyzed from the mechanistic aspect to evaluate the yield that arises from multiply damaged sites as hypothesized by Ward (Prog. Nucleic Acid Res. Mol. Biol. 35, 95-125, 1988) and Goodhead (Int. J. Radiat, Biol. 65, 7-17, 1994) as opposed to the yield that arises from single hydroxyl radicals as hypothesized by Siddiqi and Bothe (Radiat. Res. 112, 449-463, 1987). For low-LET radiation such as gamma rays, the importance of multiply damaged sites is shown to increase with the solution's hydroxyl radical scavenging capacity. For moderately high-LET radiation such as 100 keV/micron helium ions, a much different behavior is observed. In this case, a large fraction of double-strand breaks are formed as a result of multiply damaged sites over a broad range of scavenging conditions. Results also indicate that the RBE for common cellular end points correlates more closely with the RBE for multiply damaged sites than with the RBE for total double-strand breaks over a range of LET up to at least 100 keV/micron.
尽管双链断裂长期以来一直被认为是一种重要的DNA损伤类型，但已明确的是，这类广泛的损伤与细胞水平上辐射有效性的指标并无很好的相关性。双链断裂检测无法区分在单个能量沉积事件中产生的单损伤位点的复杂程度或聚集程度，而目前推测这对于理解细胞终点至关重要。作为迈向这种理解的一步，从机制方面分析了在质粒DNA中与剂量成比例形成的双链断裂，以评估如Ward（《核酸研究与分子生物学进展》35卷，95 - 125页，1988年）和Goodhead（《国际辐射生物学杂志》65卷，7 - 17页，1994年）所假设的由多重损伤位点产生的产额，与Siddiqi和Bothe（《辐射研究》112卷，449 - 463页，1987年）所假设的由单个羟基自由基产生的产额。对于低LET辐射如γ射线，多重损伤位点的重要性随溶液的羟基自由基清除能力增加而增加。对于中等高LET辐射如100 keV/微米的氦离子，观察到的行为则大不相同。在这种情况下，在广泛的清除条件范围内，很大一部分双链断裂是由多重损伤位点形成的。结果还表明，在至少100 keV/微米的LET范围内，常见细胞终点的相对生物效应（RBE）与多重损伤位点的RBE的相关性比与总双链断裂的RBE的相关性更紧密。
