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Asbestos toxicity: iron appears to be the main culprit

A team of researchers from Elettra, the Burlo Garofolo Hospital, and the University of Trieste has shed light on the mechanisms underlying the toxicity of asbestos.  This latest achievement on the part of the Trieste-based team, in collaboration with researchers from the French synchrotron ESRF and the University of Udine, is the result of an innovative analysis of lung tissue samples from patients exposed to asbestos, and highlights the key role of iron in the development of mesothelioma. The study was published in Scientific Reports, a journal of the Nature Publishing Group. The study received funding from the regional government thanks to the indications of the FVG Regional Commission on Asbestos

 

Asbestos and pleural mesothelioma: two terms that are tragically linked. The former is a mineral that was widely used in construction until a few years ago, thanks to its low cost and exceptional resistance to heat. The latter is a particularly aggressive form of pleural cancer (the pleura is the outer lining of the lungs and internal chest wall), for which exposure to asbestos is the main risk factor.
 
The danger of asbestos is due to its physical structure: its microscopic fibres are easily inhaled and can accumulate in the lungs, causing several diseases such as asbestosis (the presence of scarring in lung tissue), lung cancer, and mesothelioma. However, the precise mechanisms that explain why asbestos is such a powerful carcinogen remain to be fully understood, although the tendency of fibres to absorb nearby iron and alter its homeostasis – i.e. its balance – seems to be a fundamental driver, as shown in several previous studies .
 
“An unmistakable sign of asbestos exposure – explains Clara Rizzardi, a physician at the University of Trieste – is the formation of so-called asbestos bodies in the lung tissue. These bodies are the result of deposits of free iron, iron-storing proteins, mucopolysaccharides, and other material around asbestos fibres. Pulmonary macrophages (cells whose purpose is to defend tissue) attempt to isolate these foreign bodies by enveloping them in a sort of shell, but this also creates an enormous reservoir of iron, which can be toxic for cell DNA if present in excessive quantities and set free”.
 
In order to shed light on these mechanisms, the authors of the paper performed a series of analyses on lung tissue samples from patients exposed to asbestos. The samples came from Monfalcone hospital.
 
 “Thanks to a combination of techniques based on synchrotron light (X-ray spectroscopy and microscopy) which can photograph a sort of chemical map of the distribution of the elements present – explains Elettra’s Alessandra Gianoncelli – we found significant correlations between the chemistry and morphology of asbestos bodies and adjacent pulmonary tissue”.
 
The first object of study was iron. The analyses showed beyond a doubt that asbestos fibres and bodies cause a substantial accumulation of iron in macrophagous cells and surrounding tissue. The chemical maps traced by the researchers provided additional, key indications, both with regards to other chemical elements and by revealing the presence of various “forms” of iron.
 
“On the one hand – Gianoncelli continues – we showed that phosphorus, calcium, and magnesium also take part in the process, confirming previous findings by other researchers. On the other, we discovered for the first time that at least two types of iron are present in asbestos bodies. In addition to the expected trivalent iron, stored in ferritin, we also found significant percentages of hematite (another iron-based mineral), which we reasonably believe to be the result of the transformation of ferritin over time”.
 
“No one had ever looked at asbestos fibres in lung tissues this way, through a veritable chemical photograph - concludes Lorella Pascolo, a researcher at the Burlo Garofolo hospital - “a photograph that allows us to say that asbestos bodies are not inert structures but that, even after several years in the lungs, they continue to be a source of stress for lung tissue, due to their mobilization of iron”.
 
“These observations on the interactions of various chemical elements and on the transformations of iron in the presence of asbestos fibres in the lungs – she adds – also represent a paradigm of toxicity: a sort of reference model that can be used to understand the effects of other pollutants to which humans are currently exposed. I’m referring here to particulate matter, but as some have already pointed out, new nanomaterials could turn out to be the asbestos of the future. The data we have obtained are undoubtedly very important in helping us shed light on the pathogenic framework of asbestos-related diseases, with potential future implications from the diagnostic and therapeutic points of view as well”.


 

Scientific References: Scientific Reports 3, 24 January 2013, Article number: 1123 doi:10.1038/srep01123
“The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy”. Authors: Lorella Pascolo, Alessandra Gianoncelli, Giulia Shneider, Murielle Salomé, Manuela Schneider, Carla Calligaro, Maya Kiskinova, Mauro Melato & Clara Rizzardi. 


Last Updated on Tuesday, 06 November 2018 11:56