Epithelial Cells Expression of Ornithine Decarboxylase in Hamster Tracheal Role of Asbestos and Active Oxygen Species in Activation and Updated Version

Induction of ornithine decarbox) lase (ODC) enzyme activity occurs after exposure of hamster trachea! epithelial (HTE) cells to asbestos and the soluble tumor promoter ^-O-tetradecanoylphorbol-O-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 chrysolite or crocidolite asbestos-stimulated ODC activity occurred with simulta neous addition of catatase, 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 III), 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 (Oj and H2O2) were more proficient than OH or a halogenated oxidant. All oxidants, except HOC!, caused a significant increase in ['I I| thy mulini' 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 pro portionate to oxidant concentration and the extent of enzyme induction. Thus, data indicate that I!..<), plays a major role in asbestos-stimulated ODC induction and proliferation of epithelial cells of the respiratorytract by altering the regulation of a gene critical to proliferation.