Kinsella T J, Dobson P P, Russo A, Mitchell J B, Fornace A J
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1127-30. doi: 10.1016/0360-3016(86)90241-5.
It has been demonstrated that glutathione (GSH) depletion with buthionine sulfoximine (BSO) potentiates SR-2508 radiosensitization in hypoxic cells. We have measured the effect of SR-2508 alone, BSO alone, and combined treatment on radiation-induced DNA strand breaks in hypoxic V79 cells using alkaline and neutral elution. DNA base damage recognized by a damage specific endonuclease from M. luteus was also studied. Hypoxic irradiation markedly reduces the efficiency of single-strand (SSB) and double-strand breaks (DSB) to 10-20% compared to oxic irradiation. Hypoxia had less effect on the efficiency of base damage (ESS). BSO treatment alone, resulting in GSH depletion to less than 5% of controls, had little effect of hypoxic-SSB, DSB, and ESS. SR-2508 (5 mM) treatment alone in hypoxic cells increased the number of SSB, DSB and ESS to approximately half of that resulting from oxic irradiation. However, the combination of BSO and SR-2508 in hypoxic cells resulted in SSB and DSB comparable to oxic irradiation. This combined treatment resulted in less effect on ESS. We conclude that the observed hypoxic radiosensitization, using clonogenic survival assays with combined BSO-SR-2508, correlates with our results assessing DNA strand breaks and base damage.
已证明，用丁硫氨酸亚砜胺（BSO）消耗谷胱甘肽（GSH）可增强缺氧细胞对SR - 2508的放射增敏作用。我们使用碱性和中性洗脱法，测量了单独使用SR - 2508、单独使用BSO以及联合处理对缺氧V79细胞中辐射诱导的DNA链断裂的影响。还研究了由藤黄微球菌的损伤特异性内切酶识别的DNA碱基损伤。与有氧照射相比，缺氧照射显著降低了单链（SSB）和双链断裂（DSB）的效率至10 - 20%。缺氧对碱基损伤效率（ESS）的影响较小。单独使用BSO处理使GSH消耗至对照组的5%以下，对缺氧-SSB、DSB和ESS几乎没有影响。在缺氧细胞中单独使用SR - 2508（5 mM）处理使SSB、DSB和ESS的数量增加至有氧照射产生数量的约一半。然而，在缺氧细胞中BSO和SR - 2508联合处理导致SSB和DSB与有氧照射相当。这种联合处理对ESS的影响较小。我们得出结论，使用BSO - SR - 2508联合的克隆形成存活试验观察到的缺氧放射增敏作用，与我们评估DNA链断裂和碱基损伤的结果相关。
