Air pollution exposure, a leading cause of global mortality associated with 800,000 deaths every year, represents a major concern in cities in Europe and worldwide. Once thought to pose a threat principally to the lungs, the overall evidence on heart disease and stroke now indicates that the foremost adverse effects of air pollutants are actually on the cardiovascular system. Recent evidence indicates that air pollution exposure is associated with increased risk of VTE. Although air pollution exposure has been related with systemic inflammation, oxidative stress, and hypercoagulability, mechanisms linking inhalation of air pollutants with enhanced thrombosis and VTE are still largely unclear. Toxic metals, such as lead, arsenic, cadmium, nickel, and others, are abundant in ambient PM, often loosely bound on the particle surface, and their uptake into lung macrophages is considered a primary determinant of PM-induced inflammation. Nanoparticles are emitted from natural (e.g., volcano) and anthropic (e.g., traffic) sources, and produced via nanotechnology. Fast propagation of nanotechnologies into different industries and consumer products is causing exponential growth of nano-materials production. Hence, increasing amounts of nanoparticles reach occupational settings and the indoor and outdoor environments, thus representing a potentially serious hazard to people’s health. Although they are small solid particles, it is most useful to think of nanoparticles as a different state of matter, even from the point of view of health hazard identification and risk assessment. The risk presented by some nanoparticles may resemble that of fine and ultrafine particulate air pollution, which show an exposure-response relationship but no toxicity threshold, have the capacity to migrate in the body to reach target organs other than the lung (e.g., heart, vessels, CNS), and exert their effects on healthy subjects and not only in susceptible population subgroups. However, the mechanism by which nanoparticles interact with biological systems are relatively unknown and the toxicological, eco-toxicological and exposure data needed to perform a complete risk analysis are lacking. DNA methylation is a reversible epigenetic mechanism that, in mammals, modifies genome function through the addition of methyl groups to cytosine to form 5-methyl-cytosine (5mC). Initial results from our and other laboratories have shown that air pollution exposures induce changes in DNA methylation that can be detected in blood leukocyte DNA. Main hypothesis of the project is that PM and nanoparticles exposure may have an impact on human health, in particular through epigenetic modifications, other than through genetic alterations and biochemical pathways. To address this hypothesis we treated the A549 cell line with different doses of PM and with different doses and type of nanoparticles and we evaluated changes in gene expression focusing on inflammatory and cancer pathways. Our specific hypotheses, based not only on the literature but on preliminary data we obtained, is that PM and nanoparticles are able to trigger a cascade of events (oxidative stress, dysregulation of apoptosis, inflammation, etc) that may eventually lead to cytoxicity, genotoxic alterations and carcinogenesis. There is evidence indicating that these alterations could be determined at the epigenetic level (DNA methylation level). The translational perspective of the project is to identify hazards and assess the risks associated with exposure to PM and nanoparticles. This should assist decision makers in adopting measures suitable to avoid, or at least minimize, harm to the health and safety. In particular about nanoparticles this study could be important in assessing whether current occupational exposure limits are sufficiently protective when applied to agents that are produced or manipulated in nanoforms.
AN IN VITRO STUDY TO EVALUATE THE EPIGENETIC MODIFICATIONS INDUCED BY PARTICULATE MATTER AND NANOPARTICLES / F. Rota ; relatore: A. Bertazzi ; correlatore: A. Baccarelli. - Milano : Università degli studi di Milano. Universita' degli Studi di Milano, 2012 Feb 08. ((24. ciclo, Anno Accademico 2011.
|Titolo:||AN IN VITRO STUDY TO EVALUATE THE EPIGENETIC MODIFICATIONS INDUCED BY PARTICULATE MATTER AND NANOPARTICLES|
|Data di pubblicazione:||8-feb-2012|
|Settore Scientifico Disciplinare:||Settore MED/44 - Medicina del Lavoro|
|Citazione:||AN IN VITRO STUDY TO EVALUATE THE EPIGENETIC MODIFICATIONS INDUCED BY PARTICULATE MATTER AND NANOPARTICLES / F. Rota ; relatore: A. Bertazzi ; correlatore: A. Baccarelli. - Milano : Università degli studi di Milano. Universita' degli Studi di Milano, 2012 Feb 08. ((24. ciclo, Anno Accademico 2011.|
|Appare nelle tipologie:||Tesi di dottorato|