This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marsh, J. P. Articles by Mossman, B. T. Search for Related Content PubMed PubMed Citation Articles by Marsh, J. P. Articles by Mossman, B. T.

Role of Asbestos and Active Oxygen Species in Activation and Expression of Ornithine Decarboxylase in Hamster Tracheal Epithelial Cells¹

Department of Pathology, University of Vermont, College of Medicine, Burlington, Vermont 05405

Induction of ornithine decarboxylase (ODC) enzyme activity occurs after exposure of hamster tracheal epithelial (HTE) cells to asbestos and the soluble tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Since active oxygen species are implicated as mediators of asbestos-induced biological responses, studies here were designed to examine whether active oxygen species generated by asbestos or oxidants caused increased ODC activity. In confluent HTE cells, significant blockage of chrysotile or crocidolite asbestos-stimulated ODC activity occurred with simultaneous addition of catalase, but not superoxide dismutase, to medium. The addition of xanthine plus xanthine oxidase caused a dose-dependent increase in ODC activity, which was inhibited significantly after addition of catalase or mannitol, indicating that H₂O₂ was the principal oxidant produced in that reaction. Addition of phenazine methosulfate, a redox reagent used to generate superoxide, resulted in significant elevation of ODC, which was inhibited by addition of superoxide dismutase but not catalase. Hydrogen peroxide added to culture medium also caused a potent increase in ODC activity inhabitable by catalase. Hypochlorous acid caused increases in ODC activity, although the magnitude of this response was less than that observed with other oxidants. Therefore, although all active oxygen species examined triggered ODC, less reduced species ( and H₂O₂) were more proficient than OH or a halogenated oxidant. All oxidants, except HOCl, caused a significant increase in [³H] thymidine incorporation at 24 or 48 h after their addition to HTE cells. In comparative studies, exposure of HTE cells to either asbestos or xanthine plus xanthine oxide increased the level of ODC mRNAs proportionate to oxidant concentration and the extent of enzyme induction. Thus, data indicate that H₂O₂ plays a major role in asbestos-stimulated ODC induction and proliferation of epithelial cells of the respiratory tract by altering the regulation of a gene critical to proliferation.

¹ This work was supported by NIH Grant R01HL39469 and Pulmonary SCOR Grant PHS14212.

² To whom requests for reprints should be addressed.

Received 6/13/90. Accepted 10/12/90.

This article has been cited by other articles:

				S.-O. Yoon, S.-J. Park, S. Y. Yoon, C.-H. Yun, and A.-S. Chung Sustained Production of H2O2 Activates Pro-matrix Metalloproteinase-2 through Receptor Tyrosine Kinases/Phosphatidylinositol 3-Kinase/NF-kappa B Pathway J. Biol. Chem., August 9, 2002; 277(33): 30271 - 30282. [Abstract] [Full Text] [PDF]

				V. Levresse, A. Renier, F. Levy, V.C. Broaddus, and M.-C. Jaurand DNA breakage in asbestos-treated normal and transformed (TSV40) rat pleural mesothelial cells Mutagenesis, May 1, 2000; 15(3): 239 - 244. [Abstract] [Full Text] [PDF]

				D. W Kamp and S. A Weitzman The molecular basis of asbestos induced lung injury Thorax, July 1, 1999; 54(7): 638 - 652. [Full Text]

				M. Ding, Z. Dong, F. Chen, D. Pack, W.-Y. Ma, J. Ye, X. Shi, V. Castranova, and V. Vallyathan Asbestos Induces Activator Protein-1 Transactivation in Transgenic Mice Cancer Res., April 1, 1999; 59(8): 1884 - 1889. [Abstract] [Full Text] [PDF]

				C. V. Ramana, I. Boldogh, T. Izumi, and S. Mitra Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals PNAS, April 28, 1998; 95(9): 5061 - 5066. [Abstract] [Full Text] [PDF]