EFFECT OF RADIOPROTECTORS AND RADIOSENSITIZERS ON DNA DAMAGE PRODUCED BY X-RAYS

细胞辐射敏感性受许多因素影响，这些因素可能是 临床上很重要。 例如，细胞氧浓度和 细胞的氧化还原电位影响细胞的放射敏感性， 在临床上也很重要。 几个特工，BSO或2508，已经被 显示降低细胞中的有效巯基浓度， 作为缺氧细胞敏化剂。 添加半胱胺，另一方面 另一方面，在氧化条件下保护X射线照射的细胞。 碱性和 中性洗脱，我们测量了这些试剂对X射线的影响 诱导的DNA损伤，特别是DNA双链断裂（DSB），单 链断裂（SSB）和碱基损伤（ESS）。 我们发现缺氧 辐照显著降低了DSB和SSB的生产效率， X射线在V79细胞和降低ESS的产量在较小程度上。 当 低氧照射时BSO和2508均存在， 提高了SSB和DSB的产率，对ESS的影响较小。 辐射保护剂半胱胺使DSB产量显著降低 X射线，对SSB的影响较小，对ESS的影响很小或没有影响。 低氧辐射对DSB产率的影响最大， 辐射增敏剂或辐射保护剂半胱胺。 虽然致命的 X射线产生的病变是未知的，其他间接结果表明 DSB可能是关键病变 我们对放射增敏剂的研究， 辐射防护者支持这一假设。

Cellular radiosensitivity is affected by many factors which may be clinically important. For example, cellular oxygen concentration and the redox potential of the cell affect cellular radiosensitivity and probably are also important clinically. Several agents, BSO or 2508, have been shown to decrease the effective Sulfhydryl concentration in the cell and to act as hypoxic cell sensitizers. Addition of Cysteamine, on the other hand, protects cells x-irradiated under oxic conditions. With Alkaline and neutral elution, we have measured the effect of these agents on x-ray induced DNA damage, in particular, DNA double strand breaks (DSB), single strand breaks (SSB), and base damage (ESS). We have found that hypoxic irradiation markedly reduces the efficiency of DSB and SSB production by x-rays in V79 cells and reduces the yield of ESS to a lesser extent. When both BSO and 2508 were present during hypoxic irradiation, it markedly increased the yield of SSB and DSB, and had a lesser effect on ESS. The radioprotector Cysteamine produced a marked decrease in the yield of DSB with x-rays, had a lesser effect with SSB, and little or no effect on ESS. The yield of DSB was most affected by hypoxic irradiation, the addition of radiosensitizers, or the radioprotector Cysteamine. Although the lethal lesion produced by x-rays is unknown, indirect results of others indicate that DSB may be the critical lesion. Our work with radiosensitizers and radioprotectors support this hypothesis.