An in vivo study of the radioprotective effect of diethyldithiocarbamate (DDC).
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.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects; D004050:Ditiocarb / Q000378:metabolism / Q000627:therapeutic use*; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D013859:Thiocarbamates / Q000627:therapeutic use*; D014018:Tissue Distribution; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D013859:Thiocarbamates; D004050:Ditiocarb