Brown D M, Fisher C, Donaldson K
Department of Biological Sciences, Napier University, Edinburgh, Scotland.
J Toxicol Environ Health A. 1998 Apr 10;53(7):545-61. doi: 10.1080/009841098159132.
Synthetic vitreous fibers are in widespread use but the parameters that dictate their carcinogenicity are still a matter of scientific debate. The free radical activities of a panel comprising an asbestos sample and five different respirable synthetic vitreous fiber samples were determined, to address the hypothesis that carcinogenic fibers have greater free radical activity than noncarcinogenic fibers. On the basis of recent inhalation studies, the six samples were divided into three carcinogenic fibers-amphibole asbestos, silicon carbide, and refractory ceramic fiber 1 (designated with the abbreviation RCF 1)-and three noncarcinogenic fibers--man-made vitreous fiber 10 (a glass fiber sample designated with the abbreviation MMVF 10), Code 100/475 glass fiber, and RCF4. All experiments were carried out with equal fiber numbers. Of the two assays of free radical activity used, the plasmid assay of DNA scission showed only amosite asbestos to have free radical activity, while the salicylate assay of hydroxyl activity showed that both amosite asbestos and RCF1 release hydroxyl radicals; silicon carbide fibers had no free radical activity in either of the assays. None of the noncarcinogenic fibers demonstrated free radical activity in either of the assays. The differences in the two assays in demonstrating free radical activity with RCF1 may be due to increased release of Fe from RCF1 under the more acid conditions of the salicylate assay, which was confirmed by the fact that soluble iron caused hydroxylation of salicylate. Presence of an iron chelator inhibited the ability of the RCF1 fibers to cause hydroxylation of salicylate, demonstrating that RCF1 generates hydroxyl radical by Fenton chemical reaction in the same way as amphibole asbestos.
合成玻璃纤维被广泛使用,但决定其致癌性的参数仍存在科学争议。为了验证致癌纤维比非致癌纤维具有更高自由基活性这一假设,测定了一个由石棉样品和五个不同的可吸入合成玻璃纤维样品组成的小组的自由基活性。根据最近的吸入研究,将六个样品分为三种致癌纤维——闪石石棉、碳化硅和耐火陶瓷纤维1(缩写为RCF 1),以及三种非致癌纤维——人造玻璃纤维10(缩写为MMVF 10的玻璃纤维样品)、100/475号玻璃纤维和RCF4。所有实验均使用相同数量的纤维进行。在使用的两种自由基活性测定方法中,DNA断裂的质粒测定法仅显示铁石棉具有自由基活性,而水杨酸羟基活性测定法表明铁石棉和RCF1都能释放羟基自由基;碳化硅纤维在两种测定方法中均无自由基活性。在两种测定方法中,非致癌纤维均未显示出自由基活性。两种测定方法在显示RCF1的自由基活性方面存在差异,可能是由于在水杨酸测定法的酸性更强的条件下,RCF1中铁的释放增加,这一点通过可溶性铁导致水杨酸羟基化这一事实得到了证实。铁螯合剂的存在抑制了RCF1纤维引起水杨酸羟基化的能力,表明RCF1与闪石石棉一样,通过芬顿化学反应产生羟基自由基。