Evans R G, Engel C R, Wheatley C L, Nielsen J R, Ciborowski L J
Int J Radiat Oncol Biol Phys. 1983 Nov;9(11):1635-40. doi: 10.1016/0360-3016(83)90416-9.
We have recently shown that diethyldithiocarbamate (DDC) protects plateau-phase cultures of mammalian cells from radiation. Experiments in vivo have extended our knowledge of the radioprotective properties of DDC and show that the LD50/30 in mice is increased from 780 rad to approximately 1400 rad when non-toxic concentrations of DDC are present prior to the irradiation. When DDC is present during irradiation, the pattern of death of the mice is similar to that seen in the absence of the drug and is quite different from that seen in animals dying of a gastrointestinal syndrome (LD50/7 congruent to 1700 rad). To confirm that the LD50/30 data represent bone marrow protection by DDC, we performed bone marrow CFUS assays with and without the presence of DDC, at the time of in vivo irradiation. The DO of the CFUS is increased from 80 rad in the control animals to 120 rad in the animals that have been pretreated with DDC. In experiments using 35S-labelled DDC, the tissue distribution of the drug in tumor-bearing mice indicates a preferential uptake of DDC in kidney, lung and bone marrow compared to tumor tissue. Based on data from both in vitro and in vivo studies, we believe that DDC shows promise as a radioprotective agent and should be considered for clinical trials.
我们最近发现二乙基二硫代氨基甲酸盐（DDC）可保护处于平台期的哺乳动物细胞免受辐射。体内实验拓展了我们对DDC辐射防护特性的认识，结果显示，若在照射前给予无毒浓度的DDC，小鼠的半数致死剂量（LD50/30）可从780拉德提高至约1400拉德。若在照射期间给予DDC，小鼠的死亡模式与未给药时相似，与死于胃肠综合征（LD50/7约为1700拉德）的动物的死亡模式截然不同。为证实LD50/30数据代表DDC对骨髓的保护作用，我们在体内照射时对有或无DDC存在的情况下进行了骨髓集落形成单位-脾（CFUS）测定。CFUS的存活剂量（DO）在对照动物中为80拉德，在预先用DDC处理的动物中提高至120拉德。在使用35S标记的DDC的实验中，荷瘤小鼠体内该药物的组织分布表明，与肿瘤组织相比，DDC在肾脏、肺和骨髓中优先摄取。基于体外和体内研究的数据，我们认为DDC有望成为一种辐射防护剂，应考虑进行临床试验。
