Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytes.
Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 microg/ml of MGN for 30 min before exposure to 3 Gy of (60)Co gamma-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 microg/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 microg/ml MGN. Since the lowest MNBNC frequency was observed for 50 microg/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of gamma-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 microg/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 micro/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of (.)OH (hydroxyl), O(2) (.-) (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS(.+) (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals.
Jagetia
Ganesh Chandra
GC
Department of Radiobiology, Kasturba Medical College, Manipal 576-104, India. gc.jagetia@manipal.edu
Venkatesha
Venkatasubbaiah Ashokakumar
VA
D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000528:radiation effects; D015162:Micronucleus Tests; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
D016166:Free Radical Scavengers; D005609:Free Radicals; D011837:Radiation-Protective Agents; D044004:Xanthones; C013592:mangiferin