sbestos fibers which forms asbestos bodies.  An important initial step towards unraveling this issue is the identification and localization of the metal in native physiological environments in tissues and cells. In this respect synchrotron-based X-ray microscopy approaches are becoming very desirable tools providing correlated morphology and chemical information of the specimen. In the present study our team is trying to elucidate the very early distribution of iron, and possible other elements, in the mouse lung after asbestos exposure by means of soft X-ray imaging and X-Ray Fluorescence (XRF) microscopy (dott.ssa Lorella Pascolo-IRCCS Burlo Garofolo-Trieste/Elettra Sincrotone, Basovizza-Trieste)

Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron. Histological lung tissue examination revealed that asbestos fibers disrupt iron homeostasis in the human and mouse lung,  leading to the deposition of iron onto longer a

The mechanism of entry of asbestos fibers in the cellular compartment is currently unknown and may, at least in theory, allow the entry of asbestos fibers even in the nucleus, explaining the ability of asbestos fibers to induce alterations in DNA. We therefore planned to examine in this project, the mechanism of entry of asbestos fibers in cultured mesothelial cells and the possibility they reach the nuclear compartment. Determine if asbestos fibers (crocidolite, amosite and chrysotile) enter mesothelial cells with receptor-mediated mechanism (eg family Scavenger Receptors) or directly, in a passive way, regardless of receptors. Preliminary results obtained by ultrastructural analysis suggest that both mechanisms may be involved. The entry receptor-independent of the fibers, could allow the fibers to reach the nucleus and directly damage the DNA, causing mutations. It has been demonstrated that the DNA has a strong affinity for asbestos fibers (in particular those of chrysotile) and that once adsorbed on the fiber surface of asbestos is oxidized producing 8-hydroxy-2′-deoxyguanosine (8-OH -dG.

In this project, with the collaboration of the Department of engineering and architecture of the University of Trieste, we intend to characterize the products of the thermal treatment of the most pathogenic asbestos fibers, from the point of view of both physical-chemical and biological properties, in order to achieve the following objectives:

Develop the heat treatment most suitable for inactivating asbestos fibers and characterize the physical and chemical properties of the inactivated product. The inactivated products will be analyzed to demonstrate the loss of the structure and crystal chemistry of those surface characteristics responsible for the toxicity of the asbestos fibers (production of free radicals, chemical state of the iron).

-Determine if the inactivated asbestos fibres, compared to the untreated counterpart, lose their pathogenicity traits towards cultured mesothelial. Presently we are at the first step of the project, that is the optimization of the inactivation procedure.