In vitro study of biofunctional indicators after exposure to asbestos-like fluoro-edenite fibres (original) (raw)
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Behaviour of the new asbestos amphibole fluoro-edenite in different lung cell systems
The International Journal of Biochemistry & Cell Biology, 2004
The aim of the present research was to determine whether the recently identified and characterized new fibrous amphibole fluoro-edenite may induce a cytopathic response in cultured cells. The final goal was to gain suggestions on the potentiality of fluoro-edenite to be harmful to human beings. Epidemiological studies, in fact, have shown an excess of developing mesothelioma among residents in Biancavilla, a town in eastern Sicily located in the Etna volcanic area. Therefore, we treated human lung fibroblasts, human lung alveolar epithelial cancer cell line A549 and monocyte-macrophage cell line J774 with fluoro-edenite or crocidolite; the latter used as a highly toxic amphibole asbestos reference. Our results show that fluoro-edenite may induce functional modifications and affects some biochemical parameters in tested cell cultures in a concentration and time dependent manner. However, the observed functional modifications induced by fluoro-edenite are generally less dramatic than those induced by crocidolite and more evident on human lung alveolar epithelial cancer cell line A549 with respect to those obtained on human lung fibroblasts or monocyte-macrophage cell line J774. The sequence of the damage is hypothesised to be as follows: at increasing fluoro-edenite concentrations, and/or treatment times, the increase in reactive oxygen species (ROS) production could trigger significant DNA damage in cell cultures, concomitantly with drop in cell metabolism and increase in lactic dehydrogenase release. In conclusion, according to our data, fluoro-edenite appears as a probable carcinogenic agent, responsible for the high incidence of malignant pleural mesothelioma in Biancavilla.
2004
A total of 17 cases of pleural mesothelioma were ascertained in the town of Biancavilla (Sicily, Italy), on the southwest slopes of the volcano Etna, from 1980 to 1997. Occupational exposure to asbestos was considered possible in only 2 of them, though it could not be excluded in 5 other cases: for the remaining 10 cases the hypothesis of environmental exposure was deemed reasonable. On the basis of this evaluation, a mineralogic study was started in the area of Biancavilla, where incohesive volcanic material has largely been used in the building industry and road paving since the 1960s-1970s. This study led to the identification of the new fluoro-edenite amphibole with prismatic, acicular and fibrous asbestiform morphologies. With a view to acquiring more detailed information on the possible causal relationship between exposure to this mineral and the onset of mesotheliomas, the mineral was tested, by a single intraperitoneal or intrapleural injection, on groups of 80 Sprague-Dawley rats (40 males and 40 females) (fibrous fluoroedenite) and on a group of 30 rats (15 males and 15 females) (powdered prismatic fluoro-edenite), 8 weeks old at the start of the study, at a dose of 25 mg in 1 cc of water; 1 cc of water was administered by intraperitoneal injection to 80 rats (controls). One hundred and nine weeks after the treatment, a high incidence of peritoneal and, to a lesser extent, pleural mesotheliomas was observed in the animals treated with fibrous fluoroedenite; this incidence is comparable to that obtained with various kinds of asbestos. Up to now no cases of mesothelioma have been observed in the group treated with prismatic fluoro-edenite, or in the control group. Eur.
Effects of the new-identified amphibole fluoro-edenite in lung epithelial cells
Toxicology in vitro : an international journal published in association with BIBRA
An epidemiological survey on mortality for malignant pleural neoplasm in Italy evidenced a number of patients in Biancavilla, a village located in a volcanic area of eastern Sicily, none of which had been significantly exposed to asbestos during their professional lives. Environmental studies suggested the involvement of the material derived from stone quarries in the disease onset. A detailed crystal-chemical analysis of amphiboles contained in this material allowed the discovery and the identification of a new fiber that was named fluoro-edenite. In order to define the mode of action of fluoro-edenite at a subcellular level, we have conducted a study by using A549 cells, a tumor-cell line from a human lung carcinoma with properties of alveolar epithelial cells. The results obtained showed a remarkable tropism of A549 cells toward fluoro-edenite fibers. In fact, these epithelial cells contacted the fibers via the extension of membrane ruffles and filopodia that allowed the capture ...
Particle and Fibre Toxicology, 2014
Background An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples. Methods Primary human airway epithelial cells (HAEC) were exposed to two different LA samples as well as standard amphibole reference samples. Analysis of the samples included a complete particle size distribution analysis, calculation of surface area by electron microscopy and by gas adsorption and quantification of surface-conjugated iron and hydroxyl radical production by the fibers. Interleukin-8 mRNA levels were quantified by qRT-PCR to measure relative pro-inflammatory response induced in HAEC in re...
Toxicology in Vitro, 2006
An unusual cluster of malignant mesothelioma was evidenced in Biancavilla, a Sicily village where no inhabitant had been signiWcantly and professionally exposed to asbestos. Mineralogical and environmental studies led to the identiWcation of a new prismatic amphibole, named Xuoro-edenite. We previously reported, by using the human lung epithelial A549 cells, that prismatic Xuoro-edenite was unable to induce changes that could be somehow related to cellular transformation, and this was in accordance with studies carried out in vivo. More recently, a Wbrous amphibole with a composition very similar to that of prismatic Xuoro-edenite, was identiWed in Biancavilla. This Wbrous Xuoro-edenite was shown to induce mesothelioma in rats. In keeping with this eVect in vivo, in the present work we observed multinucleation and spreading, common features of transformed cells, as well as pro-inXammatory cytokine release in A549 cells. Such cell changes occurred without interfering with the passage of the resulting multinucleated cells through the cell cycle and without condemning cells to death. Hence, in lung epithelial cells, Wbrous Xuoro-edenite behaved similarly to the unrelated asbestos type crocidolite, whose connection with severe inXammation and cancer of the lung is renowned.
Cell Biology and Toxicology, 2011
Several asbestos-like mineral fibres, including fluoro-edenite, may cause lung cancer and/or other lung diseases. However, biological and molecular mechanisms linked to cancer development after mineral fibre exposure have not been fully investigated. In the present study, human non-malignant mesothelial (MeT-5A) and human bronchoalveolar alveolar epithelial (A549) cell lines were incubated with rising concentrations of fluoroedenite to evaluate the expression of retinoblastoma (Rb) protein, which has been demonstrated to play an important role in cell cycle control and tumour progression. Intriguingly, these results show that Rb expression was unchanged, while the level of the phosphorylated protein increased significantly in a dose-dependent manner, suggesting an involvement of this regulator protein in the pathogenesis of the lung diseases induced by mineral fibres. In conclusion, fluoro-edenite regulates the expression of phospho-retinoblastoma to trigger a network of signals strictly connected with cell proliferation and neoplastic cell transformation.
Fluoro-edenite induces fibulin-3 overexpression in non-malignant human mesothelial cells
Oncology Letters, 2016
Exposure to asbestos is associated with the development of mesothelioma. In addition to asbestos, other fibers have been identified as risk factors for malignant and non-malignant diseases of the lungs. Among these, fluoro-edenite (FE) was found in patients from Biancavilla (Sicily, Italy) with pleural and lung disease, suggesting its role for tumor expansion. In this context, the identification of early biomarkers useful for the diagnosis of cancer is mandatory. Fibulin-3 represents an important marker for the diagnosis of mesothelioma. However, it remains to be determined whether it is directly associated with exposure to asbestos-like fibers. In the present study, peripheral blood levels of fibulin-3 from 40 asbestos-exposed workers were compared with those detected in 27 street cleaners from Biancavilla. Intriguingly, the results showed that fibulin-3 levels were higher in the group of street cleaners compared with those of the asbestos-exposed workers, suggesting that these workers used the personal protective equipment according to the current regulations. These data suggest that subjects exposed to FE should be monitored for the risk of mesothelioma. FE and volcanic particulates are probably contained within dust inhaled by street cleaners from Biancavilla during their work activities. Based on these criteria, in this study, such fibers were used to treat mesothelial cells (MeT5A) in order to verify whether fibulin-3 levels are affected by these treatments. The results showed that only treatment with FE was associated with fibulin-3 overexpression at both the transcript and protein levels. It was previously demonstrated that mesothelial cells exhibited low levels of p27 following treatment with FE. Notably, p27 downregulation is associated with stathmin upregulation in cancer, conferring an aggressive phenotype of tumor cells. This observation prompted us to perform a computational evaluation demonstrating the activation of stathmin in lung cancer in patients exposed to asbestos. Overall, it can be speculated that both fibulin-3 and stathmin overexpression may be associated with the malignant transformation of mesothelial cells following exposure to asbestos-like fibers.
Toxicology and Applied Pharmacology, 1997
By using a colony-forming efficiency (CFE) assay, the cytotoxicity and proliferative potential of three mineral samples containing various proportions of fibrous talc were compared to NIEHS samples of crocidolite and chrysotile asbestos in cell types giving rise to tracheobronchial carcinomas, i.e., hamster tracheal epithelial (HTE) cells, and mesotheliomas, i.e., rat pleural mesothelial (RPM) cells. Characterization of mineralogical composition, surface area, and size distributions as well as proportions of fibers in all mineral samples allowed examination of data by various dose parameters including equal weight concentrations, numbers of fibers >5 m in length, and equivalent surface areas. Exposure to samples of asbestos caused increased numbers of colonies of HTE cells, an indication of proliferative potential, but fibrous talc did not. RPMs did not exhibit increased CFE in response to either asbestos or talc samples. Decreased numbers of colonies, an indication of cytotoxicity, were observed in both cell types and were more striking at lower weight concentrations of asbestos in comparison to talc samples. However, all samples of fibrous minerals produced comparable dose-response effects when dose was measured as numbers of fibers greater than 5 m or surface area. The unique proliferative response of HTE cells to asbestos could not be explained by differences in fiber dimensions or surface areas, indicating an important role of mineralogical composition rather than size of fibers.