Behaviour of the new asbestos amphibole fluoro-edenite in different lung cell systems (original) (raw)
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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 ...
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.
In vitro study of biofunctional indicators after exposure to asbestos-like fluoro-edenite fibres
Cellular and molecular biology (Noisy-le-Grand, France)
The in vitro biological response to fluoro-edenite (FE) fibres, an asbestos-like amphibole, was evaluated in lung alveolar epithelial A549, mesothelial MeT-5A and monocyte-macrophage J774 cell lines. The mineral has been found in the vicinity of the town of Biancavilla (Catania, Sicily), where an abnormal incidence of mesothelioma has been documented. Cell motility, distribution of polymerized actin, and synthesis of vascular endothelial growth factor (VEGF) and of beta-catenin, critical parameters for tumour development, progression and survival, were investigated in A549 and MeT-5A cells exposed to 50 microg/ml FE fibres for 24 hr and 48 hr. The levels of cyclooxygenase (COX-2) and prostaglandin (PGE2), two molecules involved in cancer pathogenesis by affecting mitogenesis, cell adhesion, immune surveillance and apoptosis, were measured in J774 cells treated with FE fibres under the same experimental conditions. Finally, FE fibres were studied by SEM and EDS analysis to investigat...
Annali dell'Istituto superiore di sanità, 2014
Amphibolic fibres with fluoro-edenitic composition characterize Biancavilla soil, including the major quarry from which building materials have been extensively extracted. These fibres induce mesothelioma in experimental animals and their in vitro biological action is similar to that of crocidolite. Malignant mesothelioma case series and incidence were examined to evaluate the disease burden on Biancavilla inhabitants. The incidence of pleural mesothelioma in Biancavilla is steadily higher than in the Sicilian Region, risk estimates are more elevated in women than in men, the most affected age class is constituted by subjects aged less than 50. Environmental exposure to fibres with fluoro-edenitic composition appears to be causally related to the elevated mesothelioma occurrence in Biancavilla. In this frame, environmental clean-up is the main goal to be pursued in public health terms. A contribution of scientific research to public health decision making with respect to priority se...
Prevention of disease caused by fluoro-edenite fibrous amphibole: the way forward
Annali dell'Istituto superiore di sanità, 2015
Few months after the publication of the monographic section of Annali dell'Istituto Superiore di Sanità second issue of 2014 "Health impact of fibres with fluoro-edenitic composition", the carcinogenicity of fluoro-edenite was assessed by the International Agency for Research on Cancer (IARC) in the frame of Monograph 111. The IARC Working Group concluded that there is sufficient evidence in humans that exposure to fluoro-edenite fibrous amphibole causes mesothelioma, and sufficient evidence of carcinogenicity in experimental animals. Fluoro-edenite was allocated to Group 1 (the agent is carcinogenic to humans). Now, in view of the recent IARC evaluation, preventive action in Biancavilla requires an upgrade. First of all, environmental monitoring has to be further implemented. All operations of house cleaning should be performed employing wet tools, in order to avoid dust-raising. It is very important that environmental and biological monitoring be related to epidemiol...
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.
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.