Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

Abstract

Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis.

Immune System and Environmental Xenobiotics - The Effect of Selected Mineral Fibers and Particles on the Immune Response

“…Potential effects of airborne fibers in humans can only occur after a complex www.intechopen.com process of inhalation, deposition, elimination, retention and translocation. The biological effects of inhaled fibers are highly dependent on dose (fiber exposure concentrationnumbers of long fibers), fiber size (diameter/length), (Donaldson & Tran, 2004;Kohyama et al, 1997;Yamato et al, 1998), durability of material in the organism (biopersistence) (Mossman et al, (2011), duration of exposure, chemical composition and properties, solubility, chemical reactivity, surface properties of the material, ability of a material to interact with body proteins etc. Host factors such as efficiency of defense mechanisms of the respiratory tract between the initial deposition and the ultimate contact of the fibers with the target cell, individual susceptibility to xenobiotics, metabolism, age, nutrition status, life style (smoking), presence of immune disease (asthma, allergic rhinitis, immunosuppression etc.)…”

Role of Macrophage-induced Inflammation in Mesothelioma

“…These tissue samples were obtained from cases throughout the United States that were sent to Dr. Suzuki for pathological review and were systematically analyzed using histology, immunohistochemistry, and electron microscopy, in some cases, over a 15-yr period. As summarized succinctly by Dumortier et al (1998) in a letter to the editor in 1998, the size and type of asbestos fibers associated with development of diffuse malignant pleural mesothelioma remain controversial (Mossman et al, 2011;Case et al, 2011;Aust et al, 2011).One possible explanation for the confusion in pleural sampling came from a pioneering study carried out by Boutin et al (1996). Using video-assisted fiber-optic thoracoscopy in eight asbestos-exposed patients and six unexposed cases, Dr. Boutin and colleagues (1996) sampled specific anatomic regions of the parietal pleura identified as collecting spots for inorganic particulates and fibers that (1996) identified numerous amphibole as well as chrysotile fibers at black spots, and 22.5% were ≥5 μm long.…”

“…(Ghio et al, 2008). In response to chronic oxidative stress, intracellular signaling pathways trigger activation of transcription factors, stimulation of cell proliferation, and resistance to apoptosis (Albrecht et al, 2004;Mossman et al, 2011).Asbestos in cell culture (Broaddus et al, 1996; Berube et al, 1996) and in some animal studies (Marchi et al, 2000) was found to induce apoptosis in mesothelial cells, and ROS may contribute to this early apoptosis (Broaddus et al, 1996); at later times, DNA or chromosomal damage may also trigger apoptosis. Presumably, it is the cells that have inherent resistance to apoptosis or acquire resistance that will survive the initial and ongoing damage to initiate multistep acquisition of genetic abnormalities that characterize tumor development (Broaddus, 1997).…”

“…In an inhalation study in rats using well-characterized aerosols and state-of-the-art methods to assess retained lung burdens, Bernstein et al (1995) found that chrysotile exposure failed to induce pleural lesions despite producing severe pulmonary fibrosis (asbestosis) and lung tumors (Mast et al, 1994). This appears to correlate with human epidemiologic studies because recent analysis suggests that most asbestos-associated mesotheliomas are due to amphibole exposure (Berman & Crump, 2008;Mossman et al, 2011).While there is a general lack of understanding of comparative pleural potency of different asbestos fiber types, a reanalysis of previous asbestos fiber inhalation studies in PR080717 / Final Progress Report APPENDIX B …”

Multi-Analytical Approach for Identifying Asbestos Minerals In Situ

“…Previous studies [15,42,43] [28]. The toxicology of chrysotile, such as tremolite asbestos, is associated with size, durability, and chemical composition [27,44,45].…”