Evans R G
Int J Radiat Oncol Biol Phys. 1985 Jun;11(6):1163-9. doi: 10.1016/0360-3016(85)90065-3.
We have established, both in vitro and in vivo, that Diethyldithiocarbamate (DDC) protects mammalian cells from radiation. The in vivo protection, when non-toxic concentrations of DDC are present one-half hour before irradiation, is reflected by a dose modification factor (DMF) of 1.9 based on LD50/30 and 1.5 using survival of CFUs as an endpoint. Further experiments in vivo have extended our knowledge to the differential radioprotective effects of DDC on the bone marrow of animals breathing room air compared to a 5.5% oxygen in nitrogen mixture. The DMF (LD50/30) for DDC in air breathing animals, previously established as 1.9, can be contrasted with a DMF, obtained in the present study, of 1.2 for animals irradiated in the hypoxic state. Moreover the DMF (CFUs survival) previously established at 1.5 for air breathing animals, can be compared to a value of 1.3, obtained in the present study, for mice irradiated under hypoxic conditions. Modification of the dose response by DDC, for both bone marrow and tumor, was also examined in animals bearing a RIF sarcoma. Although protection of the bone marrow was confirmed (DMF = 2.1), the striking finding was that the tumor cells were sensitized, in both air breathing and nitrogen breathing animals, by the addition of DDC one-half hour before the radiation exposure. Moreover, the tumor radiosensitization, a factor greater than 2, in air breathing animals, appeared to be independent of dose (D0 = 200 rad, with or without DDC). The tumor radiosensitization was even more marked in the nitrogen breathing mice, in which a factor of 10 difference in survival was noted, together with a tendency towards greater sensitization at radiation doses in the clinical range. The results, demonstrating bone marrow radioprotection by DDC (aerobic greater than hypoxic) with concomitant tumor radiosensitization (hypoxic greater than aerobic) strongly suggest a large therapeutic gain factor (TGF) which could be further explored in a clinical setting.
我们已经在体外和体内证实，二乙基二硫代氨基甲酸盐（DDC）可保护哺乳动物细胞免受辐射。当在照射前半小时存在无毒浓度的DDC时，体内保护作用表现为：基于LD50/30的剂量修正因子（DMF）为1.9，以集落形成单位（CFU）的存活率为终点时，DMF为1.5。体内的进一步实验将我们的认识扩展到了DDC对呼吸空气的动物骨髓与呼吸氮气中5.5%氧气混合气的动物骨髓的不同辐射防护作用。先前确定呼吸空气的动物中DDC的DMF（LD50/30）为1.9，与之形成对比的是，本研究中处于低氧状态下接受照射的动物的DMF为1.2。此外，先前确定呼吸空气的动物中DDC的DMF（CFU存活率）为1.5，可与本研究中低氧条件下照射的小鼠的1.3这一数值进行比较。还在携带RIF肉瘤的动物中研究了DDC对骨髓和肿瘤剂量反应的修正作用。虽然骨髓保护作用得到了证实（DMF = 2.1），但引人注目的发现是，在呼吸空气和呼吸氮气的动物中，在辐射暴露前半小时添加DDC会使肿瘤细胞敏感化。此外，呼吸空气的动物中肿瘤放射增敏作用（因子大于2）似乎与剂量无关（D0 = 200拉德，无论有无DDC）。在呼吸氮气的小鼠中肿瘤放射增敏作用更为明显，其中观察到存活率有10倍的差异，并且在临床范围内的辐射剂量下有更强的敏感化趋势。结果表明，DDC对骨髓有辐射防护作用（需氧条件下大于低氧条件下），同时伴有肿瘤放射增敏作用（低氧条件下大于需氧条件下），这强烈提示存在很大的治疗增益因子（TGF），可在临床环境中进一步探索。
