Radiation protection by disulfiram: protection of membrane and DNA in vitro and in vivo against gamma-radiation.
Disufiram (a drug used for the treatment of alcoholism) protected microsomal membranes and plasmid DNA against damages induced by gamma-radiation. The peroxidation of membrane lipids increased linearly with the radiation dose up to 600 Gy, and the presence of disulfiram inhibited membrane lipid peroxidation as assayed by the presence of thiobarbituric acid reacting substances. The reduction of the quantity of the supercoiled (ccc) form of plasmid pBR322 DNA is directly related to the radiation-induced damage, particularly to DNA strand breaks. There was a complete protection of plasmid DNA when exposed to gamma-radiation in the presence of disufiram (0.1 mM) at 300 Gy. This drug also protected deoxyribose against damages caused by hydroxyl radicals produced by the Fenton reaction. The administration of DSF to mice prior to whole-body radiation exposure (4 Gy) resulted in a reduction of peroxidation of membrane lipids in mice liver as well as a decrease in radiation-induced damage to cellular DNA, as assayed by single-cell gel electrophoresis (comet assay). The results thus suggest the possible use of DSF as a radioprotector.
Gandhi
Nitin Motilal
NM
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, India.
Gopalaswamy
Usulumarty Venu
UV
Nair
Cherupally rishnan K
Cr
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004221:Disulfiram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D011829:Radiation Dosage; D011835:Radiation Protection / Q000379:methods*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D008563:Membrane Lipids; D011837:Radiation-Protective Agents; D004247:DNA; D004221:Disulfiram