title: Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin-induced genotoxicity and decline in survival.
abstract: The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced genomic damage and alteration in the survival of cultured V79 cells. Exposure of V79 cells to bleomycin induced a concentration dependent elevation in the frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of MNBNCs were observed in the cells treated with 50 microg ml(-1) bleomycin, the highest concentration evaluated. This genotoxic effect of bleomycin was reflected in the cell survival, where a concentration dependent decline was observed in the cells treated with different concentrations of bleomycin. Treatment of cells with 1 mm naringin before exposure to different concentrations of bleomycin arrested the bleomycin-induced decline in the cell survival accompanied by a significant reduction in the frequency of micronuclei when compared with bleomycin treatment alone. The cell survival and micronuclei induction were found to be inversely correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated by exposing the cells to 10 microg ml(-1) bleomycin using single cell gel electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration of more DNA into the tails (% tail DNA) of the comets and a subsequent increase in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1 mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as indicated by a reduction in % tail DNA and OTM with increasing assessment time. A maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment, where it was 5 times lower than bleomycin alone. Our study, which was conducted on the basis of antioxidant, free radical scavenging and metal chelating properties of naringin demonstrates that naringin reduced the genotoxic effects of bleomycin and consequently increased the cell survival and therefore may act as a chemoprotective agent in clinical situations.
authors.affiliation: Department of Metallurgy, Malviya National Institute of Technology, Jaipur-302 017, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Jagetia
authors.forename: Ganesh Chandra
authors.initials: GC
authors.lastname: Jagetia
authors.forename: Shalini
authors.initials: S
authors.lastname: Jha
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay / Q000379:methods; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005347:Fibroblasts / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*
chemical_list: D016587:Antimutagenic Agents; D044950:Flavanones; D009153:Mutagens; D001761:Bleomycin; C005274:naringin