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人造矿物纤维介导的羟基自由基对DNA碱基的修饰

Hydroxyl radical mediated DNA base modification by manmade mineral fibres.

作者信息

Leanderson P, Söderkvist P, Tagesson C

机构信息

Department of Occupational Medicine, University Hospital, Linköping, Sweden.

出版信息

Br J Ind Med. 1989 Jul;46(7):435-8. doi: 10.1136/oem.46.7.435.

Abstract

Manmade mineral fibres (MMMFs) were examined for their ability to hydroxylate 2-deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OH-dG), a reaction that is mediated by hydroxyl radicals. It appeared that (1) catalase and the hydroxyl radical scavengers, dimethylsulphoxide and sodium benzoate, inhibited the hydroxylation, whereas Fe2+ and H2O2 potentiated it; (2) pretreatment of MMMFs with the iron chelator, deferoxamine, or with extensive heat (200-400 degrees C), attenuated the hydroxylation; (3) the hydroxylation obtained by various MMMFs varied considerably; (4) there was no apparent correlation between the hydroxylation and the surface area of different MMMFs, although increasing the surface area of a fibre by crushing it increased its hydroxylating capacity; and (5) there was good correlation between the hydroxylation of dG residues in DNA and the hydroxylation of pure dG in solution for the 16 different MMMFs investigated. These findings indicate that MMMFs cause a hydroxyl radical mediated DNA base modification in vitro and that there is considerable variation in the reactivity of different fibre species. The DNA modifying ability seems to depend on physical or chemical characteristics, or both, of the fibre.

摘要

对人造矿物纤维(MMMFs)将2-脱氧鸟苷(dG)羟基化为8-羟基脱氧鸟苷(8-OH-dG)的能力进行了检测,该反应由羟基自由基介导。结果显示:(1)过氧化氢酶以及羟基自由基清除剂二甲亚砜和苯甲酸钠可抑制羟基化反应,而Fe2+和H2O2则增强该反应;(2)用铁螯合剂去铁胺或高温(200 - 400摄氏度)对MMMFs进行预处理,可减弱羟基化反应;(3)不同MMMFs引发的羟基化反应差异很大;(4)不同MMMFs的羟基化反应与表面积之间无明显相关性,不过将纤维碾碎以增加其表面积会提高其羟基化能力;(5)在所研究的16种不同MMMFs中,DNA中dG残基的羟基化反应与溶液中纯dG的羟基化反应之间存在良好的相关性。这些发现表明,MMMFs在体外可导致羟基自由基介导的DNA碱基修饰,且不同纤维种类的反应活性存在显著差异。DNA修饰能力似乎取决于纤维的物理或化学特性,或两者兼而有之。

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