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 f iber (RCF1) from tile Thermal Insulation Manufacturers' Association fi ber 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 mu ch 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 gen erally not a good correlate of ability to cause free radical injury to the plasmid DNA. All fiber types caused some degree of oxidative stre ss, as revealed by depletion of intracellular GSH. Amosite asbestos up regulated nuclear binding of activator protein 1 transcription factor to a greater level than MMVF10 and RCF1; long-fiber amosite was the on ly fiber to enhance activation of the transcription factor nuclear fac tor kappa B (NF kappa B). The use of cysteine methyl ester and buthion ine sulfoximine to modulate GSH suggested that GSH homeostasis was imp ortant in leading to activation of transcription factors. We conclude that the intrinsic free radical activity is the major determinant of t ranscription factor activation and therefore gene expression in alveol ar macrophages. Although this was not related to iron release or abili ty deplete macrophage GSH at 4 hr, GSH does play a role in activation of NF kappa B.