Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells.
Protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide (tert-BOOH)- and menadione-induced DNA single strand breaks was investigated in Caco-2 cells. Both tert-BOOH and menadione induced DNA single strand breaks in a concentration-dependent manner. Pre-incubation of Caco-2 cells with either quercetin or rutin for 24 h significantly decreased the formation of DNA single strand breaks evoked by tert-BOOH (P <.05). Iron chelators, 1,10-phenanthroline (o-Phen) and deferoxamine mesylate (DFO), also protected against tert-BOOH-induced DNA damage, whereas butylated hydroxytoluene (BHT) had no effect. Quercetin, and not rutin, decreased the extent of menadione-induced DNA single strand breaks. DFO and BHT, and not o-Phen, protected against menadione-induced DNA strand break formation (P <.05). From the results of this study, iron ions were involved in tert-BOOH-induced DNA single strand break formation in Caco-2 cells, whereas DNA damage evoked by menadione was far more complex. We demonstrated that the flavonoids, quercetin and rutin, protected against tert-BOOH-induced DNA strand breaks by way of their metal ion chelating mechanism. However, quercetin, and not rutin, protected against menadione-induced DNA single strand breaks by acting as both a metal chelator and radical scavenger.
Aherne
S A
SA
Nutritional Sciences, Department of Food Science and Technology, National University of Ireland, Cork, Ireland. NOB@ucc.ie
O'Brien
N M
NM
D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D012431:Rutin / Q000494:pharmacology*; D014812:Vitamin K / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D010618:Phenanthrolines; D014812:Vitamin K; D002084:Butylated Hydroxytoluene; D012431:Rutin; D020122:tert-Butylhydroperoxide; D011794:Quercetin; D007501:Iron; D003676:Deferoxamine; C025205:1,10-phenanthroline