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评估大小分离气溶胶上结合的有机污染物复杂混合物遗传毒性的非细胞分析。第二部分:DNA 的氧化损伤。

An acellular assay to assess the genotoxicity of complex mixtures of organic pollutants bound on size segregated aerosol. Part II: oxidative damage to DNA.

机构信息

Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.

出版信息

Toxicol Lett. 2010 Oct 20;198(3):312-6. doi: 10.1016/j.toxlet.2010.06.021. Epub 2010 Jul 23.

Abstract

Ambient air particulate matter (atmospheric aerosol; PM) is an important factor in the development of various diseases. Oxidative stress is believed to be one of the mechanisms of action of PM on the human organism. The aim of our study was to investigate the ability of organic extracts of size segregated aerosol particles (EOM; three fractions of aerodynamic diameter 1-10μm, 0.5-1μm and 0.17-0.5μm) to induce oxidative damage to DNA in an in vitro acellular system of calf thymus (CT) DNA with and without S9 metabolic activation. PM was collected in the Czech Republic at four places with different levels of air pollution. Levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) tended to increase with decreasing sizes of PM. S9 metabolic activation increased the oxidative capacity of PM; mean levels of 8-oxodG/10(5) dG per 1000m(3) of air for samples with and without metabolic activation were 0.093 and 0.067, respectively (p<0.05). When results of oxidative damage to DNA were normalized per microgram of aerosol mass, mean levels of 8-oxodG/10(5) dG were 0.265 and 0.191, for incubation with and without S9 fraction, respectively (p<0.05). We observed a significant positive association between concentrations of polycyclic aromatic hydrocarbons (c-PAHs) bound to PM and levels of 8-oxodG/10(5) dG per 1000m(3) of air after metabolic activation of EOM samples (R=0.695, p<0.05). The correlation was weaker and non-significant for samples without metabolic activation (R=0.523, p=0.08). In conclusion, we showed that organic extracts of PM were able to induce oxidative damage to DNA in vitro; this ability was increased after S9 metabolic activation of EOM and with decreasing sizes of PM.

摘要

环境空气颗粒物(大气气溶胶;PM)是引发各种疾病的重要因素之一。氧化应激被认为是 PM 对人体作用的机制之一。我们的研究目的是研究大小分离气溶胶颗粒的有机提取物(EOM;三个空气动力学直径为 1-10μm、0.5-1μm 和 0.17-0.5μm 的分数)在有和没有 S9 代谢激活的小牛胸腺(CT)DNA 体外无细胞系统中诱导 DNA 氧化损伤的能力。PM 是在捷克共和国的四个空气污染程度不同的地方收集的。8-氧代-7,8-二氢-2'-脱氧鸟苷(8-oxodG)的水平随着 PM 粒径的减小而趋于升高。S9 代谢激活增加了 PM 的氧化能力;有和没有代谢激活的样品中,每 1000m3 空气中 8-oxodG/105dG 的平均值分别为 0.093 和 0.067(p<0.05)。当将 DNA 氧化损伤的结果按气溶胶质量每微克归一化时,有和没有 S9 级分孵育的 8-oxodG/105dG 的平均值分别为 0.265 和 0.191(p<0.05)。我们观察到,EOM 样品代谢激活后,与 PM 结合的多环芳烃(c-PAHs)浓度与每 1000m3 空气中的 8-oxodG/105dG 水平之间存在显著的正相关关系(R=0.695,p<0.05)。对于没有代谢激活的样品,相关性较弱且不显著(R=0.523,p=0.08)。总之,我们表明 PM 的有机提取物能够在体外诱导 DNA 氧化损伤;这种能力在 EOM 的 S9 代谢激活后以及 PM 粒径减小后增加。

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