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.
KeywordsHydrolysis Sucrose Dust DMSO Fluoride
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- Brown RC, Hoskins JA, Cole KJ, Evans CE, Sara EA (1989) Effects of asbestos fibres on some aspects of the cell second messenger system. pp. 375–381 (these proceedings).Google Scholar
- Holian A, Roney PL (1989) Superoxide anion production induced by chrysotile asbestos in the guinea pig alveolar macrophage. pp. 223–229 (these proceedings).Google Scholar
- Marsh JP, Mossman BT (1988) Mechanisms of induction of ornithine decarboxylase activity in tracheal epithelial cells by asbestiform fibers. Cancer Res 49: 709–714.Google Scholar
- Mossman BT, Cameron GS, Yotti L (1985) Cocarcinogenic and tumor promoting properties of asbestos and other minerals in tracheobronchial epithelium. In Cancer: A Comprehensive Survey: Cancer of the Respiratory Tract. Predisposing Factors. (Mass, MH et al eds) Raven Press, New York, Vol 8, pp 217–238.Google Scholar
- Perderiset M, Marsh JP, Mossman BT (1989) Asbestos activates protein kinase C in hamster tracheal epithelial cells. Submitted.Google Scholar
- Sesko AM, Cabot M, Mossman BT (1988) Accumulation of diacylglycerol precedes asbestos-induced cellular proliferation. Supp. 12E: 84.Google Scholar