Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and β-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.

In a previous work it has been demonstrated that micro-Raman spectroscopy is a technique able to recognize crystalline phases on untreated samples. In that case, inorganic particles and uncoated fibers from bronchoalveolar lavage (BAL) of a patient affected by pneumoconiosis were identified and characterized. In this work the technique is applied to asbestos bodies, that is, to coated fibers, and on crystallizations and fibrous phases observed in the plural plaque from patients affected by mesothelioma. From the Raman analysis the abundant fibrous material observed in the pleural area is talc, whereas rounded grains in the pleural tissue show the Raman spectrum of apatite, a calcium phosphate mineral particular to bones. In the pulmonary tissue many asbestos bodies, consisting of the incorporated fibers coated by iron-rich proteins, were observed. Under the 632.8 nm laser beam of the spectrometer, photo-crystallization of hematite in the iron-rich material forming the asbestos bodies can be proposed by the changes in the Raman spectra acquired during subsequent acquisitions. Nevertheless, the identification of the mineral phase constituting the incorporated fiber was possible by analyzing the Raman spectra; the results were confirmed by variable pressure scanning electron microscopy with annexed energy dispersive spectroscopy (VP-SEM-EDS) analyses.