Begg A C, Bohlken S, Bartelink H
Experimental Radiotherapy Group, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
Radiother Oncol. 1989 May;15(1):79-91. doi: 10.1016/0167-8140(89)90121-7.
The effect of the antitumour agent cisplatin on repair of X-ray-induced damage was studied in RIF1 mouse tumours treated in situ. The response of tumours, assessed by growth delay, to 4 fractions of X-rays given at 5-h intervals was compared with that after single doses. The displacement between the curves was taken as a measure of repair. A single dose of 6 mg.kg-1 cisplatin given 0.5 h before the first fraction resulted in no detectable inhibition of repair despite a significant growth delay caused by drug alone. A dose of 2 mg/kg cisplatin given 0.5 h before each of the X-ray fractions did, however, cause some repair inhibition; a result confirmed by tumour control experiments. The schedule dependence for repair inhibition was the same whether the irradiations were carried out on clamped (fully hypoxic) tumours or under ambient conditions. Significant enhancement of radiation damage was seen after correcting for the effects of drug alone, whether or not repair inhibition occurred. The effects of cisplatin on normal stroma within the tumour (vascular damage) was also investigated by monitoring the regrowth rates of recurrent tumours. In contrast to the effects on tumour cells, no enhancement of damage or inhibition of repair was seen for this assay in the combined treatment schedules.
在原位处理的RIF1小鼠肿瘤中研究了抗肿瘤药物顺铂对X射线诱导损伤修复的影响。通过生长延迟评估肿瘤对以5小时间隔给予的4次X射线照射的反应，并与单次剂量后的反应进行比较。曲线之间的位移被用作修复的指标。在第一次照射前0.5小时给予6mg/kg的单次顺铂剂量，尽管药物单独引起显著的生长延迟，但未检测到对修复的抑制作用。然而，在每次X射线照射前0.5小时给予2mg/kg的顺铂剂量确实会引起一些修复抑制；肿瘤对照实验证实了这一结果。无论照射是在钳夹（完全缺氧）肿瘤上进行还是在环境条件下进行，修复抑制的时间依赖性都是相同的。在校正药物单独作用的影响后，无论是否发生修复抑制，都观察到辐射损伤的显著增强。还通过监测复发性肿瘤的再生长速率来研究顺铂对肿瘤内正常基质（血管损伤）的影响。与对肿瘤细胞的影响相反，在联合治疗方案中，该试验未观察到损伤增强或修复抑制。
