Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling.

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.

Qi F ，Okimoto G ，Jube S ，Napolitano A ，Pass HI ，Laczko R ，Demay RM ，Khan G ，Tiirikainen M ，Rinaudo C ，Croce A ，Yang H ，Gaudino G ，Carbone M ... -  《-》

Asbestos-induced mesothelioma: is fiber biopersistence really a critical factor?

This Commentary highlights the research by Qi et al detailing the similarities and differences between crocidolite and chrysotile asbestos in terms of their transcriptional effects and transforming actions in human mesothelial cells.

Kagan E 《-》

[Expression changes of miRNAs and EMT-related genes in human mesothelial cells induced by long-term exposure to asbestos].

Li R ，Yu WK ，Wang Q ，Zhu LJ ，Zhang FF ... -  《-》

Comparative proliferative and histopathologic changes in rat lungs after inhalation of chrysotile or crocidolite asbestos.

BéruBé KA ，Quinlan TR ，Moulton G ，Hemenway D ，O'Shaughnessy P ，Vacek P ，Mossman BT ... -  《TOXICOLOGY AND APPLIED PHARMACOLOGY》

Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO(2), chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Ex

This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & amosite exposures (BD 470-715; chrysotile 495-614; crocidolite 415; amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10-13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.

Bernstein DM ，Toth B ，Rogers RA ，Kling DE ，Kunzendorf P ，Phillips JI ，Ernst H ... -  《-》