Asbestos Caused Illnesses Include Mesothelioma cancer and Cancer Of The
The introduction of asbestos caused disease can differ based on several crucial elements. One interesting study that examines this problem is known as, Asbestos-caused phosphorylation of skin growth factor receptor is related to c-fos and apoptosis by Christine L. Zanella, Cynthia R. Timblin, Andrew Cummins, Michael Jung, Jonathan Goldberg, Rachel Raabe, Thomas R. Tritton, and Brooke T. Mossman – Am J Physiol Lung Cell Mol Physiol 277 – Vol. 277, Issue 4, L684-L693, October 1999. Here’s an excerpt: We examined the systems of interaction of crocidolite asbestos fibers using the skin growth factor (EGF) receptor (EGFR) and also the role from the EGFR-extracellular signal-controlled kinase (ERK) signaling path at the begining of-response protooncogene (c-fos/c-jun) expression and apoptosis caused by asbestos in rat pleural mesothelial (Revoltions per minute) cells. Asbestos fibers, although not the nonfibrous analog riebeckite, eliminated binding of EGF towards the EGFR. It was not as a result of direct interaction of fibers with ligand, inasmuch as binding studies using fibers and EGF even without the membranes demonstrated that EGF didn’t adsorb towards the the surface of asbestos fibers. Exposure of Revoltions per minute cells to asbestos caused a more than twofold rise in steady-condition message and protein amounts of EGFR (P < 0.05).
The tyrphostin AG-1478, which inhibits the tyrosine kinase activity of the EGFR, but not the tyrphostin A-10, which does not affect EGFR activity, significantly ameliorated asbestos-induced increases in mRNA levels of c-fos but not of c-jun. Pretreatment of RPM cells with AG-1478 significantly reduced apoptosis in cells exposed to asbestos. Our findings suggest that asbestos-induced binding to EGFR initiates signaling pathways responsible for increased expression of the protooncogene c-fos and the development of apoptosis. The ability to block asbestos-induced elevations in c-fos mRNA levels and apoptosis by small-molecule inhibitors of EGFR phosphorylation may have therapeutic implications in asbestos-related diseases.
Another study is called, Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis. By I. Lemaire, H. Beaudoin, S. Mass, and C. Grondin – Am J Pathol. 1986 February 122(2): 205211. Here is an excerpt: Abstract – Asbestotic lesions are characterized by macrophagic accumulation, fibroblast proliferation, and collagen deposition. To evaluate the potential involvement of alveolar macrophages in the subsequent fibrogenic reaction, the authors studied the effects of macrophages from normal and asbestos-treated rats upon lung fibroblast proliferation in vitro. Culture supernatants from bronchoalveolar (BAL) cells (99% macrophages) of normal rats stimulated lung fibroblast DNA synthesis and growth in a dose-dependent manner. Fibroblast growth factor (FGF) release by alveolar macrophages (AMs) was rapid (within 1 hour of incubation) and dependent on the number of AMs in culture. Moreover, culture supernatants from BAL cells of animals exposed to asbestos (single intratracheal injection) stimulated fibroblast proliferation to a greater degree than culture supernatants from BAL cells of control animals. Enhanced FGF production occurred 1 week after asbestos instillation and persisted up to 24 weeks.
This change was accompanied in the early stages (1-4 weeks) by an increase in the total number of BAL cells which returned to control values by 12 weeks. Differential analysis of BAL cell populations showed a transient infiltration of neutrophils in the bronchoalveolar compartment followed by a significant accumulation of macrophages which persisted up to 1 month. Furthermore, lungs of asbestos-treated animals showed evidence of pathologic alterations characterized by fibroblast proliferation and collagen deposition. This study demonstrates that increased production of fibroblast growth factor by alveolar macrophages in vitro coincides with the development of asbestos-induced fibrosis. Prolonged stimulation of FGF release may contribute to excessive fibroblast proliferation and fibrosis.
If you found any of these excerpts, please read them in their entirety. We all owe a debt of gratitude to these researchers.