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

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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.