Photochemical reduction of ferric iron by chelators results in DNA strand breaks.
Photochemical reduction of ferric iron by chelators results in DNA strand breaks.
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螯合剂对三价铁的光化学还原导致 DNA 链断裂。
DOI：
10.1006/abbi.1993.1075
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发表时间：
1993
影响因子：
3.9
通讯作者：
Aust,AE
中科院分区：
文献类型：
--
作者：
Chao,CC;Aust,AE
研究了冷白光和黑暗条件下Fe（III）螯合物对φX174 RFI DNA单链断裂的诱导作用。在CWF光下，三价铁（25 μM）在不添加低分子量（LMW）螯合剂或添加LMW螯合剂（如柠檬酸盐、次氮基三乙酸盐（NTA）或EDTA）的情况下，分别在11%、30%、13%或0%的处理过的闭环DNA中产生SSB。添加11202使DNA SSB的形成分别增加至93、75、62或25。在黑暗条件下，无H2 O2存在时，未检测到DNA SSB。H2 O2的加入导致85%（无）、8%（柠檬酸盐）、18%（EDTA）或42%（NTA）DNA与SSB。DNA SSB的形成完全被一种强的Fe（II）特异性螯合剂ferrozine抑制。各种.OH清除剂（例如，甘露醇、5，5-二甲基-1-吡咯啉-N-氧化物、二甲亚砜）在LMW螯合剂存在下完全抑制DNA SSB形成，但在不存在下仅部分抑制。这些结果表明，Fe（II）和.OH或类似的反应物种可能参与DNA SSB的诱导。从螯合剂，如EDTA或柠檬酸盐的CO2的演变，需要CWF光和Fe（III），表明螯合剂在与Fe（III）的反应中的参与。过氧化氢酶抑制DNA SSB的形成，而超氧化物歧化酶（SOD）促进DNA SSB的形成，表明H2 O2是由O2产生的，是DNA损伤所必需的。在黑暗中，SOD抑制DNA SSB的形成，表明O2是反应所必需的，而不是H2 O2的形成。这些结果表明，在光的光化学还原的Fe（III）的螯合剂的结果在DNA SSB的形成，而无需添加H2 O2。在黑暗条件下，DNA单链断裂的形成需要加入H2 O2，这表明DNA链断裂的形成机制与此不同。
The induction of single-strand breaks (SSB) in φX174 RFI DNA by Fe(III) chelates under cool-white fluorescent (CWF) light or in darkness was investigated. Under CWF light, ferric iron (25 μM) without the addition of a low-molecular-weight (LMW) chelator or with the addition of a LMW chelator, such as citrate, nitrilotriacetate (NTA), or EDTA, generated SSB in 11, 30, 13, or 0% of the treated, closed-circular DNA, respectively. Addition of 11202 increased the formation of DNA SSB to 93, 75, 62, or 25, respectively. In the dark, DNA SSB were not detected in the absence of H2O2. The addition of H2O2resulted in 85% (none), 8% (citrate), 18% (EDTA), or 42% (NTA) DNA with SSB. The formation of DNA SSB was completely inhibited by a strong Fe(II)-specific chelator, ferrozine. Various.OH scavengers (e.g., mannitol, 5,5-dimethyl-1-pyrroline-N-oxide, dimethyl sulfoxide) completely inhibited DNA SSB formation in the presence of a LMW chelator, but only partially inhibited in the absence. These results suggest that Fe(II) and.OH or similarly reactive species may be involved in the induction of DNA SSB. The evolution of CO2from chelators, such as EDTA or citrate, required CWF light and Fe(III), suggesting the participation of chelators in the reaction with Fe(III). Under CWF light, catalase inhibited and so-peroxide dismutase (SOD) stimulated formation of DNA SSB, indicating H2O2was generated from O2and was required for DNA damage. In the dark, SOD inhibited formation of DNA SSB, suggesting O2was required for reaction(s) other than formation of H2O2. These results suggest that in the light the photochemical reduction of Fe(III) by the chelators results in formation of DNA SSB without the addition of H2O2. In the dark, the addition of H2O2was required for the formation of DNA SSB, suggesting a different mechanism for DNA strand break formation.