Kuroda Y, Yokoiyama A, Kada T
Int J Radiat Biol Relat Stud Phys Chem Med. 1975 Mar;27(3):247-57. doi: 10.1080/09553007514551541.
Radiosensitization of cultured mammalian cells was studied with halogenated pyrimidines, such as 5-iodouridine or 6-chloropurine, which have been shown to promote bacterial cell lethality when combined with gamma-irradiation. When Chinese hamster cells were exposed to gamma-rays to acidic pH values and the number of colonies was scored after 6 to 11 days of incubation, many more cells were inactivated in the presence of the drug than in its absence. This may be due to radiation-induced cytotoxic iodine radicals from the reagent in the case of 5-iodouridine, because the cells were inactivated efficiently only be contact with the previously-irradiated drug solution. The toxicity of the irradiated drug solution increased remarkably when the pH shifted to acidic side. The radiosensitization and the cytotoxic effects of gamma-irradiated drug solution were not found with 6-chloropurine. This may be the first observation on the lethal effect of chemical radicals on mammalian cells, and it is concluded that radiosensitization with 5-iodouridine does not require the drug incorporation into cellular DNA, at least under the conditions adopted in the present studies.
用卤代嘧啶,如5-碘尿苷或6-氯嘌呤,对培养的哺乳动物细胞的放射增敏作用进行了研究,这些卤代嘧啶已被证明与γ射线联合使用时可提高细菌细胞的致死率。当中国仓鼠细胞暴露于γ射线和酸性pH值环境中,并在培养6至11天后对集落数量进行计数时,与不存在药物的情况相比,存在药物时更多的细胞被灭活。对于5-碘尿苷而言,这可能是由于试剂产生的辐射诱导细胞毒性碘自由基所致,因为只有与先前照射过的药物溶液接触时细胞才会被有效灭活。当pH值向酸性一侧转变时,照射过的药物溶液的毒性显著增加。6-氯嘌呤未显示γ射线照射过的药物溶液的放射增敏和细胞毒性作用。这可能是关于化学自由基对哺乳动物细胞致死效应的首次观察,并且得出结论,至少在本研究采用的条件下,5-碘尿苷的放射增敏作用不需要药物掺入细胞DNA。