Whitaker S J, McMillan T J
Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey.
Int J Radiat Biol. 1992 Jan;61(1):29-41. doi: 10.1080/09553009214550591.
The induction of DNA double-strand breaks (dsb) following irradiation under oxygenated and hypoxic conditions with and without misonidazole was measured by pulsed-field gel electrophoresis (PFGE) in a human bladder carcinoma cell line. The dose-response curve for DNA dsb detection by PFGE was biphasic with an apparent reduction in rate of dsb induced with dose. Oxygen enhancement ratios (OER) for cell survival (at a surviving fraction of 0.1) and for DNA damage assessed by PFGE (at 80% retained) were 2.0 and 3.0 respectively. Dose-modifying factors for misonidazole (15 mM), of 1.9 (survival) and 2.4 (DNA damage) were found. Although the magnitude of the inter-experiment variations limit the precision with which cell survival and DNA electrophoresis can be compared, the data do support a simple correlation between these two measures of response. When DNA dsb induction frequency was assessed from the number average molecular weight, values of 2.7 (+/- 0.3), 0.7 (+/- 0.1) and 2.6 (+/- 0.5) x 10(-9) dsb/bp/Gy were found for irradiation under oxic, hypoxic alone and hypoxic + misonidazole conditions respectively. This gives an OER of 3.9 and a DMF of 3.7.
在人膀胱癌细胞系中，通过脉冲场凝胶电泳（PFGE）测定了在有氧和缺氧条件下，有或没有米索硝唑存在时照射后DNA双链断裂（dsb）的诱导情况。PFGE检测DNA dsb的剂量反应曲线呈双相，dsb诱导率随剂量增加而明显降低。细胞存活（存活分数为0.1时）和PFGE评估的DNA损伤（保留80%时）的氧增强比（OER）分别为2.0和3.0。发现米索硝唑（15 mM）的剂量修正因子，存活方面为1.9，DNA损伤方面为2.4。尽管实验间变化的幅度限制了细胞存活与DNA电泳比较的精度，但数据确实支持这两种反应测量之间的简单相关性。当从数均分子量评估DNA dsb诱导频率时，在有氧、单纯缺氧和缺氧+米索硝唑条件下照射，分别得到2.7（±0.3）、0.7（±0.1）和2.6（±0.5）×10⁻⁹ dsb/bp/Gy的值。这给出了3.9的OER和3.7的DMF。
