In vivo radioprotective activities of diethyldithiocarbamate (DDC)

Abstract

Studies were performed to determine whether diethyldithiocarbamate (DDC) protects against radiation damage to bone marrow, jejunal crypts, testicular tubules, hair follicles, tissues in the leg responsible for leg contractures, and a fibrosarcoma (FSA) of C 3Hf/Kam mice. In most experiments, DDC at a dose of 400 mg/kg or 1000 mg/kg body weight was given i.p. 30 minutes before single doses of gamma radiation. DDC (1000 mg/kg) given 30 minutes before whole-body irradiation protected hematopoietic stem cells by a factor (PF) of 1.59, as assessed by the LD50/30 assay, and by PFs of 1.32–1.55, as assessed by the endogenous spleen colony assay. A dose of 400 mg/kg DDC was less effective. Protection was also significant against hair loss and leg contractures; PFs produced by 1000 mg/kg DDC were 1.44 and 1.38–1.51, respectively. Jejunum was protected by 400 mg/kg DDC (PF = 1.2), but not by 1000 mg/kg. The opposite was observed with testis: 1000 mg/kg was protective (PF = 1.2), but not 400 mg/kg. DDC also protected the FSa tumor, either as lung micrometastases or as a solitary tumor in the leg. Both 400 mg/kg and 1000 mg/kg DDC protected 4 day-old micrometastases by a PF of approximately 1.1. DDC at a dose of 1000 mg/kg protected 8 mm leg tumors by a PF of 1.24 at the TCD50 level. Therefore, DDC protected both normal tissues and FSA, but the degree of protection varied greatly. A therapeutic gain was achieved in some instances.