Valavanidis Athanasios, Vlahoyianni Thomais, Fiotakis Konstantinos
University of Athens, Department of Chemistry, University Campus Zografou, 15784, Athens, Greece.
Free Radic Res. 2005 Oct;39(10):1071-81. doi: 10.1080/10715760500188671.
An association between exposure to ambient particulate matter (PM) and increased incidence of mortality and morbidity due to lung cancer and cardiovascular diseases has been demonstrated by recent epidemiological studies. Reactive oxygen species (ROS), especially hydroxyl radicals, generated by PM, have been suggested by many studies as an important factor in the oxidative damage of DNA by PM. The purpose of this study was to characterize quantitatively hydroxyl radical generation by various transition metals in the presence of H2O2 in aqueous buffer solution (pH 7.4) and hydroxylation of 2'-deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OHdG) under similar conditions. The order of metals' redox reactivity and hydroxyl radical production was Fe(II), V(IV), Cu(I), Cr(III), Ni(II), Co(II), Pb(II), Cd(II). Then, we investigated the generation of hydroxyl radicals in the presence of H2O2 by various airborne PM samples, such as total suspended particulate (TSP), PM10, PM2.5 (PM with aerodynamic diameter 10 and 2.5 microm), diesel exhaust particles (DEP), gasoline exhaust particles (GEP) and woodsmoke soot under the same conditions. When suspensions of PMs were incubated with H2O2 and dG at pH 7.4, all particles induced hydroxylation of dG and formation of 8-OHdG in a dose-dependent increase. Our findings demonstrated that PM's hydroxyl radical (HO radical) generating ability and subsequent dG hydroxylation is associated with the concentration of water-soluble metals, especially Fe and V and other redox or ionizable transition metals and not their total metal content, or insoluble metal oxides, via a Fenton-driven reaction of H2O2 with metals. Additionally, we observed, by Electron paramagnetic resonance (EPR), that PM suspensions in the presence of H2O2 generated radical species with dG, which were spin-trapped by 2-methyl-2-nitroso-propane (MNP).
近期的流行病学研究表明，暴露于环境颗粒物（PM）与肺癌和心血管疾病导致的死亡率和发病率增加之间存在关联。许多研究认为，PM产生的活性氧（ROS），尤其是羟基自由基，是PM对DNA造成氧化损伤的一个重要因素。本研究的目的是定量表征在pH 7.4的水性缓冲溶液中，各种过渡金属在H2O2存在下产生羟基自由基的情况，以及在类似条件下2'-脱氧鸟苷（dG）羟基化为8-羟基-2'-脱氧鸟苷（8-OHdG）的情况。金属的氧化还原反应活性和羟基自由基产生的顺序为：Fe(II)、V(IV)、Cu(I)、Cr(III)、Ni(II)、Co(II)、Pb(II)、Cd(II)。然后，我们在相同条件下研究了各种空气传播的PM样品，如总悬浮颗粒物（TSP）、PM10、PM2.5（空气动力学直径为10和2.5微米的颗粒物）、柴油尾气颗粒（DEP）、汽油尾气颗粒（GEP）和木烟烟灰在H2O2存在下羟基自由基的产生情况。当PM悬浮液在pH 7.4下与H2O2和dG一起孵育时，所有颗粒均以剂量依赖性增加诱导dG的羟基化和8-OHdG的形成。我们的研究结果表明，PM产生羟基自由基（HO自由基）的能力以及随后的dG羟基化与水溶性金属的浓度有关，特别是Fe和V以及其他氧化还原或可电离的过渡金属，而不是它们的总金属含量或不溶性金属氧化物，这是通过H2O2与金属的芬顿驱动反应实现的。此外我们通过电子顺磁共振（EPR）观察到，在H2O2存在下的PM悬浮液与dG产生了自由基物种，这些自由基被2-甲基-2-亚硝基丙烷（MNP）自旋捕获。
