Oxidative damage to DNA constituents by iron-mediated Fenton reactions: the deoxyadenosine family
Oxidative damage to DNA constituents by iron-mediated Fenton reactions: the deoxyadenosine family
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DOI：
10.1080/07391102.2012.682206
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Goswami, Bhaswati
中科院分区：
文献类型：
--
作者：
Chattopadhyaya, Rajagopal;Goswami, Bhaswati
研究了在存在和不存在乙醇或NADH的情况下，将2 '-脱氧腺苷（dA）、5'-dAMP、3 '-dAMP、达帕、dA（pdA）（19）和聚（dA）：寡聚（dT）暴露于铁/H2 O2的影响。HPLC保留时间，酶处理，放射性标记的底物，紫外吸收光谱，和快原子轰击质谱（FABMS）已被用来区分20个产品所产生的反应，其中16个已被确定和4个端基异构体提出的比较与早期的γ辐射研究。负责反应的自由基似乎类似于辐射衍生的（OH）-O-中心点，有许多共同的产物，但有一些新的可能是专门针对芬顿诱导的损伤。两个新的二聚体加合物所产生的羟胺在N7和随后的缩合与两个已知的糖损伤产物，dR-腺嘌呤-N1-氧化物，和两个异构体的dR-FAPy所产生的自由基攻击在C4和C5，可能被认为是新的在本研究中。与辐射衍生的（OH）-O-中心点不同，所研究的自由基由于其在基底分子附近产生而难以消除。有人提出，铁结合到磷酸基团，并在其附近产生自由基。由芬顿反应产生的dA（pdA）（11）中的链断裂有两种类型，自发的和碱不稳定的。双链体DNA对这种自由基的攻击不太敏感，因为它的各种降解产物是用单体底物获得的那些降解产物的子集，并且与来自其他底物的那些相比，对于poly（dA）：oligo（dT），仅dR-FAPy产生相对增强。
The effect of exposing 2'-deoxyadenosine (dA), 5'-dAMP, 3'-dAMP, dApA, dA(pdA)(19), and poly(dA): oligo(dT) to iron/H2O2 in the presence and absence of ethanol or NADH has been studied. HPLC retention times, enzyme treatments, radiolabeled substrates, UV absorption spectra, and fast atom bombardment mass spectrometry (FABMS) have been used to distinguish 20 products arising from the reaction, of which 16 have been identified and four anomers proposed by comparison with earlier gamma radiation studies. The radical responsible for the reactions seems to be analogous to radiation-derived (OH)-O-center dot, has many products in common, but has some novel ones probably specific for Fenton-induced damage. Two new dimeric adducts arising from the generation of hydroxylamine at N7 and its subsequent condensation with two known sugar damage products, dR-adenine-N1-oxide, and two isomers of dR-FAPy arising from radical attacks at C4 and C5, may be considered novel in the present study. Unlike radiation-derived (OH)-O-center dot, the radical under study is difficult to eliminate due to its generation in the proximity of the substrate molecules. It is proposed that the iron binds to the phosphate group and generates the radical in its vicinity. Strand breaks in dA(pdA)(11) resulting from the Fenton reaction are of two types, spontaneous and alkali-labile. Duplex DNA is less sensitive to attack by this radical, as its various degradation products are a subset of those obtained with monomer substrates and only dR-FAPy production is relatively enhanced for poly (dA): oligo (dT) as compared to those from other substrates.