Environmental Health Perspectives 105, Supplement 5, September 1997

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Free Radical Activity of Industrial Fibers: Role of Iron in Oxidative Stress and Activation of Transcription Factors

Peter S. Gilmour, 1 David M. Brown, 1 Paul H. Beswick, 1 William MacNee, 2 Irfan Rahman, 2 and Kenneth Donaldson 1

1 Department of Biological Sciences, Napier University, Edinburgh, United Kingdom
2 Rayne Laboratory, Unit of Respiratory Medicine, University of Edinburgh, Edinburgh, United Kingdom

Abstract
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 Fe 3+ was released than Fe 2+ 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. -- Environ Health Perspect 105(Suppl 5):1313-1317 (1997)

Key words : asbestos, fiber, MMVF, RCF, free radicals, oxidative stress, glutathione, transcription factors

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 27 March 1997; accepted 11July 1997.

We acknowledge the help of W. Nicholson in this study and the Health and Savety Executive for their support of DMB.

Address correspondence to Dr. P.S. Gilmour, Applied Chemical and Physical Sciences, Napier University, 10 Colinton Road, Edinburgh EH10 5DT, UK. Telephone: 0131 455 2505. Fax: 0131 455 2290. E-mail: p.gilmour@napier.ac.uk

Abbreviations used: AP-1, activator protein 1; BSO, buthionine sulfoximine; CME, cysteine methyl ester; DSF-B, desferrioxamine-B; GSH, reduced glutathione; GSSG, oxidized glutathione; LFA, long-fiber amosite; LPS, lipopolysacharride; Man, mannitol; MMVF, man-made vitreous fiber(s); NF kappa B, nuclear factor kappa B; RCC, Research and Consulting Company; RCF, refractory ceramic fiber(s); TIMA, Thermal Insulation Manufacturers' Association.

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Last Update: November 21, 1997