Verheye-Dua F, Böhm L
Radiation Oncology Department, Stellenbosch University, Tygerberg, South Africa.
Radiat Oncol Investig. 1998;6(3):109-19. doi: 10.1002/(SICI)1520-6823(1998)6:3<109::AID-ROI1>3.0.CO;2-1.
Two normal, two tumour, one transformed fibroblast cell line established from Ataxia telangiectasia (AT) patients and one corrected AT hybrid were characterised with regard to alpha, beta, SF2, and D values. Survival of 60Co gamma-irradiated tumour and transformed cells was markedly reduced when the Na+, K+-ATPase inhibitor ouabain was present 1 hr before and 3 hr post irradiation. Under these conditions, the radiosensitivity in normal cells remained virtually unchanged. Suppression of repair was found to play a role in the ouabain-induced inhibition of the cell survival. In A549 lung carcinoma cells, addition of 10(-8) M ouabain decreases the sublethal damage recovery ratio from 56.5 to 13.3. The same drug concentration decreases the recovery ratio in L132 epithelial cells only from 5.1 to 4.9. The fast repair component, as measured over the first 1.5 hr after irradiation, decreases from 1.83 to 0.36 hr(-1) in A549 cells and from 0.35 to 0.16 hr(-1) in HeLa cells. For 2 Gy fractions, the presence of 10(-8) M ouabain 1 hr before irradiation and 3 hr after irradiation induces dose enhancement ratios of 1.15-1.5. A more pronounced effect on cell inactivation may be expected from multiple fractions. The concentrations required to downregulate sublethal damage repair fall within the range where cardiac glycosides are used clinically. Application of these drugs in radiotherapy thus seems feasible.
对来自共济失调毛细血管扩张症（AT）患者建立的两株正常细胞系、两株肿瘤细胞系、一株转化成纤维细胞系以及一株校正后的AT杂交细胞系进行了α、β、SF2和D值的表征。当在照射前1小时和照射后3小时存在Na +，K + -ATP酶抑制剂哇巴因时，60Coγ射线照射的肿瘤细胞和转化细胞的存活率显著降低。在这些条件下，正常细胞的放射敏感性几乎保持不变。发现修复抑制在哇巴因诱导的细胞存活抑制中起作用。在A549肺癌细胞中，添加10（-8）M哇巴因可使亚致死损伤恢复率从56.5降至13.3。相同的药物浓度仅使L132上皮细胞的恢复率从5.1降至4.9。在照射后的前1.5小时测量的快速修复组分，在A549细胞中从1.83降至0.36小时（-1），在HeLa细胞中从0.35降至0.16小时（-1）。对于2 Gy分次照射，在照射前1小时和照射后3小时存在10（-8）M哇巴因可诱导剂量增强比为1.15 - 1.5。多次分次照射可能会对细胞失活产生更明显的影响。下调亚致死损伤修复所需的浓度处于临床上使用强心苷的范围内。因此，这些药物在放射治疗中的应用似乎是可行的。
