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苯胺脾脏毒性中的铁释放与氧化性DNA损伤

Iron release and oxidative DNA damage in splenic toxicity of aniline.

作者信息

Wu Xiaohong, Kannan Subburaj, Ramanujam V M Sadagopa, Khan M Firoze

机构信息

Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.

出版信息

J Toxicol Environ Health A. 2005 Apr 23;68(8):657-66. doi: 10.1080/15287390590921757.

Abstract

Mechanisms by which aniline produces selective toxicity to the spleen are not well understood. Previously, studies showed that aniline exposure induces lipid peroxidation and protein oxidation in the spleen. The present study was aimed to determine the release of free iron and oxidative DNA damage in the spleen following aniline exposure. To achieve this, male SD rats were orally administered 1 mmol/kg/d aniline for 7 d, while controls received the vehicle only. Total splenic iron content showed a significant increase of 200% in the aniline-treated rats, whereas free iron (low-molecular-weight chelatable iron) showed a marked increase of 375% in comparison to controls. Oxidative DNA damage, measured in terms of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, showed a remarkable increase of 83% in the aniline-treated rats. These results suggest an association between release of free iron and oxidative DNA damage, which could lead to mutagenic and/or carcinogenic responses in the spleen.

摘要

苯胺对脾脏产生选择性毒性的机制尚未完全明确。此前的研究表明,接触苯胺会诱导脾脏中的脂质过氧化和蛋白质氧化。本研究旨在确定苯胺暴露后脾脏中游离铁的释放以及氧化性DNA损伤情况。为此,将雄性SD大鼠按1 mmol/kg/d的剂量口服给予苯胺,持续7天,而对照组仅给予赋形剂。与对照组相比,苯胺处理组大鼠的脾脏总铁含量显著增加了200%,而游离铁(低分子量可螯合铁)则显著增加了375%。以8-羟基-2'-脱氧鸟苷(8-OHdG)水平衡量的氧化性DNA损伤在苯胺处理组大鼠中显著增加了83%。这些结果表明游离铁的释放与氧化性DNA损伤之间存在关联,这可能导致脾脏中的诱变和/或致癌反应。

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