<p>Analyzing biological and molecular characteristics and genomic damage induced by exposure to asbestos</p>

Abstract

Asbestos is one of the most important occupational carcinogens. Currently, about 125 million people worldwide are exposed to asbestos in the workplace. According to global estimates, at least 107,000 people die each year from lung cancer, mesothelioma, and asbestosis as a result of occupational exposure to asbestos. The high pathogenicity of this material is currently known, being associated with the development of pulmonary diseases, of which lung cancer is the main cause of death due to exposure to this mineral. Pulmonary diseases related to asbestos are a common clinical problem and a major health concern worldwide. Extensive research has identified many important pathogenic mechanisms; however, the precise molecular mechanisms involved, and the generated genomic damage that lead to the development of these diseases, are not completely understood. The modes of action that underlie this type of disease seem to differ depending on the type of fiber, lung clearance, and genetics. This evidences the need to increase our knowledge about these effects on human health. This review focuses on the characteristics of asbestos and the cellular and genomic damage generated in humans via exposure.

Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma

“…Asbestos is one of the most important occupational carcinogens. 1 Malignant pleural mesothelioma (MPM) is an aggressive and lethal asbestos-related malignancy that arises from the mesothelial lining of the pleura. [2][3][4] The incidence of deaths due to mesothelioma have been increasing, even though the use of asbestos in the workplace is currently prohibited in Western countries.…”

Asbestos and Intrahepatic Cholangiocarcinoma

“…In line with this observation, epigenetic silencing of CDKN2A gene, that encodes the tumor suppressors p16(INK4A) and p14(ARF), has been reported as an early and key molecular event occurring during the latency period between exposure to long asbestos fibers and cell malignant transformation [12]. Chronic inflammation generated by the prolonged phagocytic activity in order to eliminate biopersistent fibers also induce the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by activated macrophages [10]. ROS and RNS are known to promote cell malignant transformation by induction of DNA single/double strand breaks, DNA base modifications, formation of DNA adducts, lipid peroxidation and activation of signalling cascades involved in cell proliferation and survival [10].…”

“…Indeed as macrophages may reach 10-20 µm diameter, fibers longer 20 µm cannot be completely phagocytosed, thus leading to incomplete or 'frustrated' phagocytosis, characterized by the prolonged release of pro-inflammatory cytokines by activated macrophages [9]. Asbestos-induced chronic inflammation may activate multiple signaling cascades involved in cell proliferation and survival, including the epidermal growth factor receptor (EGFR) pathway [10]. Moreover sustained inflammatory signals may cause alterations in the cellular epigenetic program and induce gene hypermethylation [11].…”

“…Chronic inflammation generated by the prolonged phagocytic activity in order to eliminate biopersistent fibers also induce the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by activated macrophages [10]. ROS and RNS are known to promote cell malignant transformation by induction of DNA single/double strand breaks, DNA base modifications, formation of DNA adducts, lipid peroxidation and activation of signalling cascades involved in cell proliferation and survival [10]. ROS and RNS release in target tissues in turn recruit other macrophages and inflammatory cells at the sites of fiber deposition, thus sustaining the prolonged production of free radicals and chronic inflammation [10].…”

“…ROS and RNS are known to promote cell malignant transformation by induction of DNA single/double strand breaks, DNA base modifications, formation of DNA adducts, lipid peroxidation and activation of signalling cascades involved in cell proliferation and survival [10]. ROS and RNS release in target tissues in turn recruit other macrophages and inflammatory cells at the sites of fiber deposition, thus sustaining the prolonged production of free radicals and chronic inflammation [10]. Asbestos fibers may promote ROS and RNS production also via Fenton reaction, as some types of amphiboles contain iron as integral components of their chemical structure, whereas other types of fibers as surface impurity [13]; notably, crocidolite and amosite fibers are particularly iron-rich, containing 20%-30% iron by weight.…”