Gilmour P S, Beswick P H, Brown D M, Donaldson K
Department of Biological Sciences, Napier University, Edinburgh, UK.
Carcinogenesis. 1995 Dec;16(12):2973-9. doi: 10.1093/carcin/16.12.2973.
The ability of a number of respirable industrial fibres, amosite and crocidolite asbestos, refractory ceramic fibres (RCFs) and man-made vitreous fibres (MMVFs) to cause free radical injury to plasmid phi X174 RFI DNA was assessed. The oxidative DNA damage was observed as depletion of supercoiled DNA after fibre treatment was quantified by scanning laser densitometry. The mechanism of fibre-mediated damage was determined by the use of the specific hydroxyl radical scavenger mannitol and the iron chelator desferrioxamine-B. The amosite and crocidolite asbestos caused substantial damage to DNA that was dose-related. The free radicals responsible for the asbestos-mediated DNA damage were hydroxyl radicals, as determined by inhibition with mannitol. Asbestos fibre-mediated damage to DNA was completely ameliorated by the chelation of fibre-associated iron with desferrioxamine-B. The amount of Fe(II) and Fe(III) released by equal numbers of the different fibre types at equal fibre number was determined. The fibres released very small amounts of Fe(II) and there were no significant differences between the fibre types. The fibres released substantial amounts of Fe(III); MMVF 21 released significantly more Fe(III) than any of the other fibres and short fibre amosite also released more Fe(III) than three of the MMVFs and two of the RCFs. When ability to release Fe(II) and Fe(III) was compared with ability to cause DNA damage there was not a good correlation, because only the long amosite and crocidolite caused substantial free radical injury to DNA; this contrasts with MMVF 21 and short amosite being the two fibres that released the greatest amounts of iron. The loss of ability to damage DNA in DSF-B-treated asbestos fibres shows that iron at the surface of asbestos fibres definitely has a role in generating hydroxyl radicals. However, it is clear that some fibres, such as short amosite and MMVF 21, release large quantities of iron without causing free radical damage, whilst neither long amosite nor crocidolite released more iron than the other fibres. The exact role of iron in fibre reactivity therefore remains unresolved, but fibre-bound iron not released from the surface of asbestos could be important. Further research is under way to investigate this possibility.
评估了多种可吸入工业纤维、铁石棉和青石棉、耐火陶瓷纤维（RCF）以及人造玻璃纤维（MMVF）对质粒φX174 RFI DNA造成自由基损伤的能力。通过扫描激光密度测定法定量纤维处理后超螺旋DNA的消耗，以此观察氧化DNA损伤。使用特定的羟基自由基清除剂甘露醇和铁螯合剂去铁胺-B来确定纤维介导损伤的机制。铁石棉和青石棉对DNA造成了与剂量相关的实质性损伤。通过甘露醇抑制作用确定，导致石棉介导DNA损伤的自由基是羟基自由基。用去铁胺-B螯合纤维相关铁后，石棉纤维介导的DNA损伤完全得到改善。测定了相同数量的不同纤维类型在相同纤维数量下释放的Fe(II)和Fe(III)的量。这些纤维释放的Fe(II)量非常少，不同纤维类型之间没有显著差异。这些纤维释放了大量的Fe(III)；MMVF 21释放的Fe(III)明显多于其他任何一种纤维，短纤维铁石棉释放的Fe(III)也比三种MMVF和两种RCF多。当比较释放Fe(II)和Fe(III)的能力与造成DNA损伤的能力时，没有良好的相关性，因为只有长铁石棉和青石棉对DNA造成了实质性的自由基损伤；这与MMVF 21和短铁石棉是释放铁量最大的两种纤维形成对比。在去铁胺-B处理的石棉纤维中，损伤DNA的能力丧失表明石棉纤维表面的铁肯定在产生羟基自由基中起作用。然而，很明显，一些纤维，如短铁石棉和MMVF 21，释放大量的铁却不造成自由基损伤，而长铁石棉和青石棉释放的铁并不比其他纤维多。因此，铁在纤维反应性中的确切作用仍未解决，但未从石棉表面释放的纤维结合铁可能很重要。正在进行进一步的研究来调查这种可能性。
