Gilmour P S, Brown D M, Beswick P H, MacNee W, Rahman I, Donaldson K
Department of Biological Sciences, Napier University, Edinburgh, United Kingdom.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1313-7. doi: 10.1289/ehp.97105s51313.
We studied asbestos, vitreous fiber (MMVF10), and refractory ceramic fiber (RCF1) from the Thermal Insulation Manufacturers' Association fiber repository regarding the following: free radical damage to plasmid DNA, iron release, ability to deplete glutathione (GSH), and activate redox-sensitive transcription factors in macrophages. Asbestos had much more free radical activity than any of the man-made vitreous fibers. More Fe3+ was released than Fe2+ and more of both was released at pH 4.5 than at pH 7.2. Release of iron from the different fibers was generally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stress, as revealed by depletion of intracellular GSH. Amosite asbestos upregulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the only fiber to enhance activation of the transcription factor nuclear factor kappa B (NF kappa B). The use of cysteine methyl ester and buthionine sulfoximine to modulate GSH suggested that GSH homeostasis was important in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of transcription factor activation and therefore gene expression in alveolar macrophages. Although this was not related to iron release or ability to deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.
我们从隔热材料制造商协会的纤维库中研究了石棉、玻璃纤维（MMVF10）和耐火陶瓷纤维（RCF1），涉及以下方面：对质粒DNA的自由基损伤、铁释放、消耗谷胱甘肽（GSH）的能力以及激活巨噬细胞中氧化还原敏感转录因子的能力。石棉的自由基活性比任何一种人造玻璃纤维都高得多。释放出的Fe3+比Fe2+多，且在pH 4.5时两种离子的释放量都比在pH 7.2时多。不同纤维中铁的释放与对质粒DNA造成自由基损伤的能力通常没有很好的相关性。如细胞内GSH的消耗所示，所有纤维类型都会引起一定程度的氧化应激。铁石棉上调激活蛋白1转录因子的核结合水平高于MMVF10和RCF1；长纤维铁石棉是唯一能增强转录因子核因子κB（NF-κB）激活的纤维。使用半胱氨酸甲酯和丁硫氨酸亚砜胺调节GSH表明，GSH稳态在导致转录因子激活方面很重要。我们得出结论，内在自由基活性是转录因子激活以及因此肺泡巨噬细胞中基因表达的主要决定因素。虽然这与4小时时的铁释放或消耗巨噬细胞GSH的能力无关，但GSH确实在NF-κB的激活中起作用。
