Effects of Asbestos on Specific Binding of Phorbol Ester Tumor Promoter and Protein Kinase C Activity in Hamster Tracheal Epithelial (HTE) Cells
Crocidolite asbestos causes proliferative changes in tracheobronchial epithelial cells that are similar to those observed after exposure of a number of cell types to phorbol esters, i.e. classical tumor promoters in skin and other organs (reviewed in Mossman et al., 1985). These biological changes, which include increased uptake of 3H-thymidine (Landesman and Mossman, 1982), increased activity of ornithine decarboxylase (ODC), i.e. a rate-limiting enzyme in the biosynthesis of polyamines (Marsh and Mossman, 1988), and the development of squamous metaplasia (Mossman et al., 1980a), may be important in the pathogenesis of bronchogenic carcinoma, a tumor of high risk in asbestos workers who smoke. In an attempt to understand how asbestos initiates alterations in cell proliferation and differentiation, we focused here on whether crocidolite asbestos causes activation of protein kinase C (PKC), a calcium- and phospholipid-dependent enzyme which phosphorylates several intracellular protein substrates and plays a crucial role in growth control and tumor promotion (Nishizuka, 1986). The potent phorbol tumor promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA), and related compounds activate PKC by structurally resembling diacylglycerol.
KeywordsOrnithine Decarboxylase Squamous Metaplasia Hamster Tracheal Epithelial Crocidolite Asbestos PHORBOL Ester Tumor Promoter
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