Zhou P K, Sproston A R, Marples B, West C M, Margison G P, Hendry J H
Cancer Research Campaign Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Radiother Oncol. 1998 Jun;47(3):271-6. doi: 10.1016/s0167-8140(97)00200-4.
To study the correlation of residual DNA double-strand breakage after irradiation and cellular radiosensitivity in cells showing marked differences in radiosensitivity.
The levels of DNA double-strand breaks remaining at 4 h after irradiation were measured by graded-voltage gel electrophoresis in fibroblast cell strains derived from seven individuals either with normal radiosensitivity (n = 2), or with genetic abnormalities known to show increased (two ataxia telangiectasia, one scid) or possibly decreased (two Li-Fraumeni family members) sensitivity.
The slope of the dose-response curve for DNA breaks remaining unrepaired at 4 h showed a highly significant correlation with cellular radiosensitivity characterized by SF2, alpha, or D (r > or = 0.91, P < 0.001). Hence, this measure of genotoxic damage was predictive of radiation sensitivity for cells affected by a variety of mutations in different damage signalling/repair components.
This correlation confirms another published study and extends it to cell lines with other genetic defects. The technique may be useful in the development of rapid assays to predict the sensitivity of normal tissues in patients receiving radiotherapy.
研究在放射敏感性存在显著差异的细胞中，照射后残留的DNA双链断裂与细胞放射敏感性之间的相关性。
采用梯度电压凝胶电泳法，测定来自7名个体的成纤维细胞系在照射后4小时残留的DNA双链断裂水平。这些个体中，2名具有正常放射敏感性，2名患有共济失调毛细血管扩张症，1名患有严重联合免疫缺陷病，其放射敏感性已知会增加，另外2名李-弗劳梅尼综合征家族成员的放射敏感性可能降低。
4小时时未修复的DNA断裂剂量反应曲线的斜率与以SF2、α或D表征的细胞放射敏感性高度显著相关（r≥0.91，P<0.001）。因此，这种遗传毒性损伤的测量方法可预测受不同损伤信号传导/修复成分中各种突变影响的细胞的放射敏感性。
这种相关性证实了另一项已发表的研究，并将其扩展到具有其他遗传缺陷的细胞系。该技术可能有助于开发快速检测方法，以预测接受放疗患者正常组织的敏感性。
