Environmental Health Perspectives 105, Supplement 5, September 1997

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Possible Role of Lipid Peroxidation in the Induction of NF- kappa B and AP-1 in RFL-6 Cells by Crocidolite Asbestos: Evidence following Protection by Vitamin E

Stephen P. Faux and Peter J. Howden

Institute of Occupational Health, University of Birmingham, Edgbaston, Birmingham, United Kingdom

Abstract
Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF- kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF- kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF- kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF- kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF- kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF- kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events leading to NF- kappa B transcription factor induction by asbestos. -- Environ Health Perspect 105(Suppl 5):1127-1130 (1997)

Key words : lipid peroxidation, asbestos, NF- kappa B, AP-1

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 26 March 1997; accepted 11 April 1997.

We thank the Colt Foundation and the U.K. Health and Safety Executive for financial support.

Address correspondence to Dr. S.P. Faux, MRC Toxicology Unit, Hodgkin Building, University of Leicester, P.O. Box 138, Lancaster Road, Leicester, LE1 9HN, U.K. Telephone: 0116 252 5622. Fax: 0116 252 5616. E-mail: spf7@leicester.ac.uk

Abbreviations used: AA, arachidonic acid; AP-1, activator protein-1; ETYA, 5,8,11,14-eicosatetraynoic acid; 4-HNE, 4-hydroxynonenal; NDGA, nordihydroguaiaretic acid; NF- kappa B, nuclear factor kappa B; RFL-6, rat lung fibroblast cell line; ROS, reactive oxygen species.

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Last Update: October 17, 1997