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Pulmonary endpoints (lung carcinomas and asbestosis) following inhalation exposure to asbestos Mossman BT; Lippmann M; Hesterberg TW; Kelsey KT; Barchowsky A; Bonner JCJ Toxicol Environ Health B Crit Rev 2011[]; 14 (1-4): 76-121Lung 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.|Animals[MESH]|Asbestos/administration & dosage/chemistry/pharmacokinetics/*toxicity[MESH]|Asbestosis/*metabolism[MESH]|Biological Transport[MESH]|Body Burden[MESH]|Carcinogens, Environmental/administration & dosage/chemistry/pharmacokinetics/toxicity[MESH]|Carcinoma/*chemically induced/genetics/metabolism[MESH]|Chemical Phenomena[MESH]|Humans[MESH]|Inhalation Exposure/*adverse effects[MESH]|Lung Neoplasms/*chemically induced/genetics/metabolism[MESH]|Lung/*drug effects/metabolism[MESH]|Mineral Fibers/analysis/toxicity[MESH]|Mutagens/administration & dosage/chemistry/pharmacokinetics/toxicity[MESH]|Particulate Matter/administration & dosage/chemistry/pharmacokinetics/*toxicity[MESH]|Tissue Distribution[MESH] |
