Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors.
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.
Gilmour
P S
PS
Department of Biological Sciences, Napier University, Edinburgh, United Kingdom. p.gilmour@napier.ac.uk
Brown
D M
DM
Beswick
P H
PH
MacNee
W
W
Rahman
I
I
Donaldson
K
K
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019016:Mineral Fibers / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D002273:Carcinogens; D005609:Free Radicals; D019016:Mineral Fibers; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D001194:Asbestos; D007501:Iron; D005978:Glutathione