A closer look at the toxicity mechanisms of erionite, a major natural carcinogen

Erionite is a naturally occurring zeolite, a crystalline material characterized by a framework of silicon/aluminium-centred tetrahedra, joined together by means of the oxygen atoms at the vertices. The open framework contains channels and cavities (micropores) that accommodate varying amounts of exchangeable H2O molecules and extra-framework cations, such as sodium, calcium, magnesium, potassium.

Figure 1 from the top-story by Raneri et al., Environmental Research. 252, 118878 (2024).

Figure 1: High resolution TEM image of an erionite bundle (courtesy E. Mugnaioli).

Erionite is found in nature in the form of bundles of very thin fibres (Figure 1), the appearance of which resembles a wad of wool (“erion” in Greek means wool) and, much more rarely, as individual needle-like fibres. Erionite has caused exceptional cancer (malignant mesothelioma) morbidity in some areas of Cappadocia (Turkey) and is now classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen. In fact, erionite’s high biopersistence—its ability to remain in the body without breaking down—combined with its unique ion-exchange properties, makes it one of the major natural hazards.

A collaboration between Elettra, the Universities of Modena and Reggio Emilia, Genova and Parma, and the Italian National Research Council has made significant strides in understanding the toxicity mechanisms of erionite. In a groundbreaking study, the team employed cutting-edge synchrotron-based micro-X-ray fluorescence (micro-XRF) and micro-X-ray absorption spectroscopy to investigate how erionite-Na interacts with human macrophages, the immune cells responsible for engulfing and digesting foreign particles.

The study revealed that when macrophages engulf erionite fibres, there is a significant disruption in the balance of intracellular calcium and sodium ions. This disruption is crucial as it triggers harmful cellular responses, potentially leading to cancer-promoting adverse effects.

Surprisingly, the anticipated major role of erionite’s ion-exchange capacity in toxicity was found to be less significant than previously thought. Instead, the internalization of iron-rich particles associated with erionite fibres and the subsequent cellular stress play a more critical role. These findings help clarify why erionite is much more potent in causing malignant mesothelioma than other mineral fibres like asbestos. The study employed soft X-ray microscopy combined with low energy sub-micro-XRF mapping at the TwinMic beamline of Elettra Sincrotrone Trieste complemented by measurements taken at the ID21 beamline of ESRF Synchrotron in Grenoble, France.

Figure 2 from the top-story by Raneri et al., Environmental Research. 252, 118878 (2024).

Figure 2: Absorption (Abs), differential Phase Contrast (PhC) images and corresponding Mg and Na XRF maps in macrophages exposed to erionite after a) 8 h, b) 24 h, c) 96 h of contact with the fibres. Scale bars are 10 μm.

The findings revealed a fascinating timeline of erionite interaction with cells. Initially, smaller fibres and iron-rich particles were preferentially phagocytosed within 8 h of exposure. By 24 h, longer fibres began to be internalized, and by 96 h, all fibres and particles were engulfed, leaving no free fibres on the cell surface and on the cell support (Figure 2). The analyses also indicated a slight release of sodium from the mineral fibres early in the exposure, which became more pronounced at intermediate times but less evident after 96 h. Magnesium, on the other hand, remained co-localized with the fibres and associated particles throughout the exposure period, with no detectable release (Figure 2).

This research not only advances our understanding of erionite’s toxicity but also underscores the importance of ongoing investigations into the environmental and health impacts of mineral fibres. The insights gained from this study could pave the way for developing better protective measures for individuals exposed to these hazardous materials.

This research was conducted by the following research team:

Simona Raneri1, Alessandra Gianoncelli2, Valentina Bonanni2, Serena Mirata3, Sonia Scarfì3, Laura Fornasini4, Danilo Bersani4, Debora Baroni5, Cristiana Picco5 and Alessandro F. Gualtieri6
1 CNR-ICCOM, National Research Council, Institute of Chemistry and OrganoMetallic Compounds, Pisa, Italy.
2 Elettra - Sincrotrone Trieste S.C.p.A., Trieste, Italy.
3 Dep. of Earth, Environment and Life Sciences, University of Genova, Genova, Italy.
4 Dep. of Mathematical, Physical and Computer Sciences, University of Parma, Parma, Italy.
5 Istituto di Biofisica, CNR, Genova, Italy.
6 Dep. of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.

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Reference

S. Raneri, A. Gianoncelli, V. Bonanni, S. Mirata, S. Scarfì, L. Fornasini, D. Bersani, D. Baroni, C. Picco and A. F. Gualtieri; "PThe influence of cation exchange on the possible mechanism of erionite toxicity: A synchrotron-based micro-X-ray fluorescence study on THP-1-derived macrophages exposed to erionite-Na", Environmental Research. 252, 118878 (2024); DOI: 10.1016/j.envres.2024.118878.

 
Last Updated on Monday, 10 June 2024 12:15