Inflammatory Disorders and the Increased Occurrence of Mesothelioma

A better understanding of asbestos related diseases is necessary if we are ever to find a cure to Mesothelioma.?? One interesting study is called, "Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases." By J Jagirdar, T C Lee, J Reibman, L I Gold, C Aston, R Bégin, and W N Rom - Environ Health Perspect. 1997 September; 105(Suppl 5): 1197–1203.?? Here is an excerpt: "Abstract - Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases."

A second study is called, "Asbestos and Benzo(a)pyrene Synergism in the Transformation of Syrian Hamster Embryo Cells" by Joseph A. DiPaolo, Anthony J. DeMarinis, Jay Doniger - Pharmacology 1983;27:65-73.?? Here is an excerpt: "Abstract - Four varieties of asbestos fibers, crocidolite, anthophyllite, amosite, and chrysotile, induced a low rate of morphologic transformation in Syrian hamster cells. Of the four tested, chrysotile was the most lethal as reflected by colony survival. When cells were exposed to 1 μg of benzo(a)pyrene (BP)&slash;l ml medium or 3 J/m2 ultraviolet irradiation and to different concentrations of the asbestos fibers, an enhancement of transformation occurred only with BP. The enhancement was dose responsive with all fiber species except for amosite which was dose independent. The synergistic activity of BP and asbestos suggests that asbestos facilitates the transport of BP to the cell site(s) critical for transformation. These results provide a basis for investigating the carcinogenic and cocarcinogenic potential of asbestos fibers in mammalian cells."

Another interesting study is called, "Interaction of asbestos with alveolar cells" by Yasunosuke Suzuki - Environ Health Perspect. 1974 December; 9: 241–252.?? Here is an excerpt: "Abstract - A number of electron microphotographs are presented showing the various aspects of phagocytosis of fibers in lung tissue.?? The fibers were rapidly phagocytosed by alveolar macrophages, by polymorphonuclear leucocytes, and less frequently by alveolar epithelial cells. They were also found in the cytoplasm of the alveolar stromal macrophages. In the late stage of the disease, macrophages containing the minerals were recognized in the fibrous submesothelial connective tissues. In this stage, a cell intermediate in structure between the epithelial cell and the macrophage was observed in the alveolar lining. This cell showed strong phagocytic activity against the fibers.The process of phagocytosis of the fibers was quite similar to that of other microparticles such as Thorotrast and India ink. It had been suggested that phagosomes containing the fibers became transformed into secondary lysosomes.The fate of the phagocytosed fibers varied. Some were partly dissolved or digested with marked reduction in the thickness of the wall of the chrysotile fibril. Many became coated by hemosiderin which accumulated in the cytoplasm of the phagocytic cells. This coating transformed the fibers into asbestos bodies. Finally many fibers were released because of the death of the host cell. Uncoated fibers as well as various stages of phagocytosis were observed in all animals, including those 1 to 2 years after the instillation of asbestos. This strongly suggests that fibers may be repeatedly phagocytosed, released and ephagocytosed, inducing a continuous response of the alveolar cells and maintaining the disease."

We all owe a debt of gratitude to these fine researchers for their hard work and dedication.?? If you found any of these excerpts interesting, please read the studies in their entirety.

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