Evaluation of diethyldithiocarbamate as a radioprotector of bone marrow

The radioprotective action of DDC on normal hematopoietic tissue in mice was evaluated. An increase in CFU-S and CFU-GM in DDC treated unirradiated control mice was consistently observed. When post-irradiation survival of CFU-S and CFU-GM from DDC treated animals was normalized to account for this observed increase, protection factors ranging from 0.9 to 1.6 were observed. These protection factors are significantly lower than those reported by others. Maximum radioprotection was observed when irradiations were performed 15 to 30 min after DDC treatment; maximum increase in GFU-GM occurred within one to two hr following treatment. The increase in CFU-GM is analogous to that observed in animals treated with endotoxin, a non-thiol radioprotector. When C3H/HeJ mice, which are genetically incapable of responding to endotoxin, were challenged with DDC, an average CFU-GM increase of 1.7 times was observed, suggesting that the stimulatory effects of DDC were not due to endotoxin contamination. DDC was administered daily for three days before irradiation and little or no increase in CFU-GM and no radioprotection was observed, suggesting that the marrow can become refractory to DDC. When WR-2721 was tested in similar studies, a dose-modifying radioprotection was observed, with no significant non-specific stimulation of hematopoietic cells.