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

细胞的辐射敏感性受到许多因素的影响，这些因素可能是 临床上很重要。例如，细胞内O2浓度和氧化还原 细胞的潜力影响细胞的辐射敏感性，可能是 在临床上也很重要。几种代理，BSO或2508，已经被证明 降低细胞内的有效巯基浓度，并起到 低氧细胞敏感剂。另一方面，添加半胱胺， 在有氧条件下保护经X-射线照射的细胞。含碱性和 中性洗脱，我们测量了这些试剂对x射线的影响。 诱导DNA损伤，特别是DNA双链断裂(DSB)，单链 链断裂(SSB)和碱基损伤(ESS)。我们已经发现了低氧 辐照显著降低了DSB和SSB的生产效率 X射线照射V79细胞，并在较小程度上降低ESS的产量。什么时候 在低氧照射过程中，BSO和2508均存在，明显 增加了SSB和DSB的产量，对ESS的影响较小。这个 辐射保护剂半胱胺显著降低了DSB的产量 X射线对SSB的影响较小，对ESS的影响很小或没有影响。 DSB的产量受低氧照射的影响最大，添加 辐射增敏剂，或辐射防护剂半胱胺。尽管致命的 X射线造成的损伤尚不清楚，其他间接结果表明 DSB可能是关键病变。我们在放射增敏剂和 辐射防护器支持这一假设。

Cellular radiosensitivity is affected by many factors which may be clinically important. For example, cellular O2 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.