Radiation protection by diethyldithiocarbamate: protection of membrane and DNA in vitro and in vivo against gamma-radiation.
Diethyldithiocarbamate (DDTC) is studied for its antioxidant and radioprotective abilities. DDTC at a concentration of 0.5 mM reduced DPPH radical. DDTC reduced the damage to deoxyribose resulting from hydroxyl radicals generated by Fenton reaction, indicating that the radioprotective abilities of this compound could be due to the free radical scavenging. DDTC protected rat liver microsomal membranes in vitro from peroxidative damage in lipids (measured as TBARS) resulting from 50 Gy gamma-radiation. It also protected plasmid pBR322 DNA from radiation-induced strand breaks. An oral administration of DDTC to mice before whole body gamma-radiation exposure (4 Gy) resulted in a reduction of radiation-induced lipid peroxides in the liver homogenates. An administration of DDTC to mice before gamma-radiation reduced the radiation-induced DNA damage as studied by single cell gel-electrophoresis (comet assay). The comet parameters such as tail length, tail moment, and percent of DNA in tail were found to increase in the blood leukocytes of mice exposed to 4 Gy gamma-radiation. When DDTC was administered to mice before the radiation exposure, the increase in the comet parameters as a result of radiation was prevented, indicating a protection of cellular DNA. The present study has implication for the potential use of DDTC as a radioprotector.
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India.
Nitin Motilal
NM
Gandhi
Cherupally Krishnan Krishnan
CK
Nair
D000284:Administration, Oral; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D002478:Cells, Cultured; D020552:Comet Assay; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D004249:DNA Damage; D004050:Ditiocarb / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D011835:Radiation Protection / Q000379:methods*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D011837:Radiation-Protective Agents; D004247:DNA; D004050:Ditiocarb