@article {10520, title = {Puzzling Results from Germline Mutations Analysis in a Group of Asbestos-Exposed Patients in a High-risk Area of Northeast Italy.}, journal = {Anticancer Res}, volume = {37}, year = {2017}, month = {2017 06}, pages = {3073-3083}, abstract = {

BACKGROUND: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM.

MATERIALS AND METHODS: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma.

RESULTS: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10\%).

CONCLUSION: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings.

}, keywords = {Aged, Aged, 80 and over, Asbestos, Environmental Exposure, Female, Germ-Line Mutation, Humans, Italy, Lung Neoplasms, Male, Mesothelioma, Middle Aged, Risk, Tumor Suppressor Proteins, Ubiquitin Thiolesterase}, issn = {1791-7530}, doi = {10.21873/anticanres.11663}, author = {Rizzardi, Clara and Athanasakis, Emmanouil and Cammisuli, Francesca and Monego, Simeone Dal and DE Spelorzi, Yeraldin Chiquinquira Castillo and Costantinides, Fulvio and Giudici, Fabiola and Pinamonti, Maurizio and Canzonieri, Vincenzo and Melato, Mauro and Pascolo, Lorella} } @article {1936, title = {Peroxidase-like activity of ferruginous bodies isolated by exploiting their magnetic property.}, journal = {J Toxicol Environ Health A}, volume = {75}, year = {2012}, month = {2012}, pages = {603-23}, abstract = {

Ferruginous bodies (FB) are polymorphic structures whose formation is macrophage dependent, and are composed of a core, which may consist of an asbestos fiber coated with proteins, among which ferritin is the main component. Within ferritin, the ferric and ferrous ions are coordinated as ferrihydrite, which is the main iron (Fe) storage compound. However, when ferritin accumulates in some tissues following Fe overload it also contains magnetite along with ferrihydrite, which endows it with magnetic properties. Recently studies showed that magnetite exerts peroxidase-like activity, and since ferruginous bodies display magnetic properties, it was postulated that these particular structures may also contain magnetite within the ferritin coating, and thus may also exert peroxidase-like activity. Histochemical analysis for peroxidase of isolated FB smears demonstrated positive staining. Samples isolated from 4 different autopsy lung fragments were also able to oxidize 3,3{\textquoteright},5,5{\textquoteright}-tetramethyl-benzidine to a blue colored compound that absorbs at 655 nm. This activity was (1) azide and heat insensitive with optimal pH from 5 to 6, and (2) highly variable, changing more than 25-fold from one sample to another. These findings, together with evidence that the peroxidase-like activity of ferruginous bodies has a hydrogen peroxide and substrate requirement different from that of human myeloperoxidase, can exclude that this enzyme gives a significant contribution to the formation of FB. Standard Fe-rich asbestos fibers also express a peroxidase-like activity, but this appears negligible compared to that of ferruginous bodies. Strong acidification of standard Fe-containing asbestos fibers or magnetically isolated ferruginous bodies liberates a high amount of peroxidase-like activity, which is probably accounted for by the release of Fe ions. Further, FB also damage mesothelial cells in vitro. Data suggest that FB exert peroxidase-like activity and cytotoxic activity against mesothelial cells, and hence may be an important factor in pathogenesis of asbestos-related diseases.

}, keywords = {Air Pollutants, Occupational, Asbestos, Asbestosis, Benzidines, Catalysis, Cell Line, Chromogenic Compounds, Cytotoxins, Ferric Compounds, Ferritins, Ferrosoferric Oxide, Humans, Hydrogen-Ion Concentration, Lung, Magnetic Phenomena, Mesothelioma, Mineral Fibers, Oxidation-Reduction, Peroxidases, Respiratory Mucosa}, issn = {1528-7394}, doi = {10.1080/15287394.2012.688478}, author = {Borelli, Violetta and Trevisan, Elisa and Vita, Francesca and Bottin, Cristina and Melato, Mauro and Rizzardi, Clara and Zabucchi, Giuliano} }