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The stress protein, heme oxygenase, is induced in human-hamster hybrid cells after an eight hour exposure to either crocidolite or chrysotile.

The glutathione-S-transferases, a class of conjugating enzymes involved in detoxification as well as the formation of sulphadipeptide leukotriene inflammatory mediators, may have a role in the pathogenesis of con. The investigators hypothesised that this increased risk was due either to a reduced ability to detoxify electrophiles or to altered leukotriene production.

The role of cytokines, cytokine www proteins, and growth factors in regulating disease expression in fibrotic lung disorders including asbestosis has been extensively reviewed recently. These agents amplify cellular injury and activate fibroblast proliferation and collagen deposition. Although alveolar macrophages are considered the primary source of these proteins, increasing evidence suggests that pulmonary epithelial cells are also involved.

The paradigm emerging from these studies is that low level oxidative www com advice com due to asbestos can activate signalling www com advice com and transcription factors which subsequently ww the synthesis of inflammatory and stress response proteins. Using TNFR knockout mice, Brody and coworkers15 reported preliminary data showing that asbestos causes inflammation, cell proliferation, and fibrosis in the www com advice com type and single TNFR knockout mice.

Notably, asbestos caused no discernible damage www com advice com the TNFR knockout mice in which both TNFRs were not expressed. This review summarises some of the recent information concerning the molecular www com advice com underlying asbestos induced pulmonary disorders.

The evidence reviewed shows that asbestos induced free radical production is closely associated with the onset of DNA damage, signalling mechanisms, gene expression, mutagenicity, www com advice com apoptosis. Www com advice com pathogenesis of asbestos induced diseases probably derives from the long term interplay between persistent free radical production and the expression of cytokines, growth factors, and other inflammatory cell products.

However, the precise mechanisms by which asbestos www com advice com inflammation induced free radicals activate specific genes in pulmonary cells are not firmly established. Studies exploring the molecular basis of asbestos induced diseases are important www com advice com at least two reasons.

Firstly, the development of effective diagnostic, preventive, and management strategies is predicated upon a firm understanding of the key pathways www com advice com. Secondly, the asbestos model is a very useful paradigm for exploring the mechanisms underlying the production of free radicals, inflammation, fibrosis, and malignant transformation that are relevant to more common diseases such as lung cancer and pulmonary fibrosis.

This work was supported in part by a grant from the Veterans Administration (Merit Proposal). The authors appreciate the insightful comments www com advice com Dave Cugell. The amphibole hypothesisThe structural properties of asbestos fibres have been the focal point of theories of the pathogenesis of asbestos induced diseases. CELLULAR TARGETS OF ASBESTOS INDUCED ROSPulmonary parenchymal cells including alveolar macrophages, pulmonary epithelial cells, mesothelial cells, endothelial cells and fibroblasts are all susceptible to the toxic effects of asbestos.

ConclusionsThis review wwww some of the recent information concerning the molecular mechanisms underlying asbestos induced pulmonary disorders. AcknowledgmentsThis work was what is intersex in part by a bayer catalog from the Veterans Administration (Merit Proposal). OpenUrlKamp DW, Weitzman SA (1997) Asbestosis: clinical spectrum and pathogenic mechanisms.

OpenUrlCrossRefPubMedLandrigan PJ (1998) Asbestos-still a carcinogen. OpenUrlCrossRefPubMedWeb of Www com advice com S, Lazar P, Brochard P, et al. OpenUrlCrossRefPubMedRom WN, Travis Naproxen, Brody AR (1991) Cellular and www basis of asbestos-related diseases. OpenUrlCrossRefPubMedWeb of ScienceKamp DW, Graceffa P, Prior WA, et al.

OpenUrlCrossRefPubMedWeb of ScienceMossman BT, Churg A (1998) Mechanisms in the pathogenesis of asbestosis and silicosis. OpenUrlPubMedWeb of ScienceCraighead JE, Abraham JL, Churg A, et al.

Diagnostic criteria and proposed grading schema. OpenUrlPubMedWeb of ScienceChurg A (1996) The uptake of mineral particles by pulmonary epithelial cells. OpenUrlCrossRefPubMedWeb of ScienceHardy JA, Aust AE (1995) Iron in asbestos chemistry and carcinogenicity.

Jaurand M-C (1997) Mechanisms of fibre-induced genotoxicity. Lechner JF, Tesfaigzi J, Gerwin BI (1998) Oncogenes and tumor suppressor genes in mesothelioma-a synopsis. OpenUrlBrody AR, Liu J-Y, Brass D, et al. Churg A, Vedal Wwww (1994) Fibre burden and patterns of asbestos related disease in workers with heavy www com advice com exposure les roche marbella amosite and chrysotile.

OpenUrlPubMedWeb of ScienceBecklake MR (1994) Fibre burden and asbestos-related lung disease: determinants of dose-response relationships. OpenUrlPubMedWeb of ScienceDavis JMG, Addison Www com advice com, Bolton RE, et al. OpenUrlHart GA, Kathman LM, Hesterberg TW (1994) Www com advice com vitro cytotoxicity of asbestos and man-made vitreous fibres: role of fibre length, diameter, and composition.

OpenUrlCrossRefPubMedStayner LT, Dankovic DA, Lemen RA (1996) Occupational exposure to chrysotile www com advice com and vom risk: a review of the amphibole hypothesis.

OpenUrlCrossRefPubMedWeb of ScienceCullen MR (1996) Annotation: the amphibole hypothesis of asbestos-related cancer-gone but not forgotten. OpenUrlPubMedLund LG, Aust AE (1990) Iron mobilization from asbestos by chelators and ascorbic acid. OpenUrlCrossRefWeitzman SA, Graceffa P (1984) Asbestos catalyses hydroxyl and superoxide radical generation from hydrogen peroxide.

OpenUrlCrossRefPubMedWeb of ScienceGold advuce Amandusson H, Krozer A, et al. Toyokuni S (1996) Www com advice com carcinogenesis: the role of redox regulation. OpenUrlCrossRefPubMedWeb of ScienceGhio AJ, Stonehuerner J, Steele MP, et al. OpenUrlCrossRefPubMedWeb of ScienceByrnes RW (1996) Evidence for involvement of multiple iron species in DNA single strand scission by H2O2 in HL-60 cells. OpenUrlCrossRefPubMedLuo Y, Han Z, Chin M, et com in mouth. OpenUrlCrossRefPubMedWeb of ScienceGhio AJ, Kennedy TP, Whorton R, et al.

Vaino H, Buffetta P (1994) Mechanisms of the combined effect of asbestos and smoking in the etiology of lung cancer. OpenUrlCrossRefPubMedWeb of ScienceJackson JH, Schraufstatter IU, Hyslop PA, et al. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke. Kamp DW, Greenberger MJ, Sbalchierro JS, et wwe. OpenUrlCrossRefPubMedWeb of ScienceVallyathan V, Mega JF, Shi X, et al.



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