Radiation-induced micronucleus formation and DNA damage in human lymphocytes and their prevention by antioxidant thiols.
Thiol family of antioxidants has been considered to be the most effective class of radio protective agents. Present study reports a comparative evaluation of antioxidant thiols, namely N-acetyl cysteine (NAC), glutathione (GSH) and thioproline (TP), on gamma radiation-induced damage to human lymphocytes DNA as assessed by micronucleus (MN) formation and comet assay parameters. Pretreatment of cells with NAC, GSH and TP showed significant protection against DNA damage and MN frequency in irradiated lymphocytes (2-4 Gy). The magnitude of DNA damage protection was found to be concentration dependent (100-300 microM) which followed the order GSH>NAC>TP. Further, antioxidant thiols mediated protection against DNA damage in irradiated lymphocyte showed significant correlation with their ability to decrease intracellular ROS but not to the increase in intracellular GSH. Experiments on the effect of antioxidant thiols on plasmid DNA irradiated under cell free aqueous conditions showed that NAC exerts greater protection than GSH against radiation damage. TP showed similar responses in cellular and plasmid DNA. Greater protection of plasmid DNA by NAC is ascribable to its more potential hydrogen donor ability as revealed by radical chromogen 2,2-diphenyl-1-picrylhydrazyl (DPPH) photometric assay. Thus, present study indicated that radioprotection of lymphocytes DNA by antioxidant thiols are closely correlated to the reduction of cellular oxidative stress, which seems to involve multiple mechanisms.
Tiwari
Prabha
P
Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
Kumar
Amit
A
Balakrishnan
S
S
Kushwaha
H S
HS
Mishra
K P
KP
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D005720:Gamma Rays; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007958:Leukocyte Count / Q000706:statistics & numerical data; D008214:Lymphocytes / Q000187:drug effects*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced* / Q000706:statistics & numerical data; D015162:Micronucleus Tests; D018384:Oxidative Stress; D011827:Radiation; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014466:Ultraviolet Rays
D000975:Antioxidants; D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds; D004247:DNA; D005978:Glutathione; D000111:Acetylcysteine