Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione induced DNA single strand breaks in Caco-2 cells

Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione induced DNA single strand breaks in Caco-2 cells
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DOI:
10.1016/s0891-5849(00)00360-9
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发表时间:
2000-09-15
影响因子:
7.4
通讯作者:
O'Brien, NM
O'Brien, NM
中科院分区:
医学1区
文献类型:
--
作者:
Aherne, SA;O'Brien, NM

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在Caco-2细胞中研究了黄酮类化合物槲皮素和芦丁对叔丁基过氧化氢(叔-BOOH)和甲萘醌诱导的DNA单链断裂的保护作用。叔丁氧羰基和甲萘醌均以浓度依赖性方式诱导DNA单链断裂。Caco-2细胞与槲皮素或芸香苷预孵育24小时可显着减少叔丁基羟基乙醇引起的DNA单链断裂的形成(P < .05)。铁螯合剂,1,10-菲咯啉(邻菲咯啉)和甲磺酸去铁胺(DFO),也防止叔丁基羟基甲苯(BHT)诱导的DNA损伤,而没有效果。槲皮素,而不是芦丁,降低甲萘醌诱导的DNA单链断裂的程度。DFO和BHT,而不是邻菲咯啉,保护对甲萘醌诱导的DNA链断裂形成(P <0.05)。从这项研究的结果来看,铁离子参与了Caco-2细胞中叔丁基羟基诱导的DNA单链断裂形成,而甲萘醌引起的DNA损伤要复杂得多。我们证明,黄酮类化合物,槲皮素和芦丁,防止叔丁基羟基诱导的DNA链断裂的方式,其金属离子螯合机制。然而,槲皮素,而不是芦丁,保护对甲萘醌诱导的DNA单链断裂作为金属螯合剂和自由基清除剂。(C)2000 Elsevier Science Inc.
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. (C) 2000 Elsevier Science Inc.