Morton J D, Porter E, Yabuki H, Nath R, Rockwell S
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510-8040.
Radiat Res. 1990 Nov;124(2):178-82.
The effects of the combination of a perfluorochemical emulsion (Fluosol DA, 20%) and carbogen (95% O2, 5% CO2) on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation were examined. Tumors were irradiated locally in unrestrained, unanesthetized rats at a dose rate of 0.98 Gy/h, using a specially designed 241Am irradiator system. Cell survival was measured using a colony formation assay. The tumor cell survival curves were fitted to linear relationships of the form ln S = - alpha D, where alpha for air-breathing rats was 0.104 +/- 0.005 Gy-1, as compared to 0.137 +/- 0.009 Gy-1 for rats treated with Fluosol plus carbogen. The increase in the slope of the survival curve produced by the treatment with Fluosol and carbogen was highly significant with a P value of 0.0015. The radiosensitization factor for the combination of Fluosol/carbogen plus continuous low-dose-rate irradiation was 1.32 +/- 0.11. Slightly less radiosensitization was observed with continuous low-dose-rate irradiation than in previous experiments using acute high-dose-rate irradiation. The diminished sensitization with Fluosol/carbogen during continuous low-dose-rate irradiation probably reflects the intrinsically lower oxygen enhancement ratio (OER) of low-dose/low-dose-rate irradiation, reoxygenation of the tumors during the prolonged treatment times used for continuous low-dose-rate irradiation, and the decrease in the levels of circulating perfluorochemicals during the 30-h irradiations. More importantly, the significant level of radiosensitization observed in the experiments with continuous low-dose-rate irradiation suggests that hypoxic cells persist in BA1112 tumors during continuous low-dose-rate irradiations and that the response of these tumors to continuous low-dose-rate irradiation can be improved by adjunctive treatments which oxygenate these radioresistant hypoxic tumor cells.
研究了全氟化学乳剂（氟索DA，20%）与卡波金（95%氧气，5%二氧化碳）联合应用对BA1112大鼠横纹肌肉瘤在连续低剂量率照射下反应的影响。使用专门设计的241Am辐照系统，以0.98 Gy/h的剂量率对未约束、未麻醉大鼠的肿瘤进行局部照射。采用集落形成试验测量细胞存活率。肿瘤细胞存活曲线拟合为ln S = -αD形式的线性关系，其中呼吸空气的大鼠的α为0.104±0.005 Gy-1，而接受氟索加卡波金治疗的大鼠的α为0.137±0.009 Gy-1。氟索和卡波金治疗导致的存活曲线斜率增加非常显著，P值为0.0015。氟索/卡波金联合连续低剂量率照射的放射增敏因子为1.32±0.11。与之前使用急性高剂量率照射的实验相比，连续低剂量率照射观察到的放射增敏作用略小。连续低剂量率照射期间氟索/卡波金增敏作用减弱可能反映了低剂量/低剂量率照射固有的较低氧增强比（OER）、连续低剂量率照射所用延长治疗时间内肿瘤的再氧合以及30小时照射期间循环全氟化学物质水平的降低。更重要的是，在连续低剂量率照射实验中观察到的显著放射增敏水平表明，在连续低剂量率照射期间BA1112肿瘤中存在缺氧细胞，并且这些肿瘤对连续低剂量率照射的反应可以通过使这些抗辐射缺氧肿瘤细胞充氧的辅助治疗得到改善。
