Erionite exposure in North Dakota and Turkish villages with mesothelioma

Abstract

Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30- to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.

Fig. 1.

Erionite deposits in the United States and roads with erionite-containing gravel in Dunn County, North Dakota.

Fig. 2.

Similar physical and chemical characteristics of erionite from North Dakota and Cappadocia, Turkey. (A) Scanning electron microscopy images with the 50-μm bar scale at Upper Left shows that fibers from (i) ND and (ii) Turkey are similar both in length and width. For both, maximum length is about 50 μm, whereas widths range well below 1 μm. Mechanical abrasion would be expected to reduce both dimensions. (B) Atomic Si/(Si+Al) vs. Frequency for ND and Turkey erionite. Turkey erionite appears to be slightly richer in Si but there is considerable overlap for the two locations. (C) A classic ternary diagram showing a compositional comparison of ND and Turkey erionite on the basis of atoms. These analyses have been adjusted for calculated Na and K loss and thus appear closer to the K vertex relative to no corrections.

Fig. 3.

Similar biological activity of erionite from North Dakota and Cappadocia, Turkey. (A) HM cells were cocultured with macrophages and exposed to either erionite or glass beads (control). After 6–8 wk of culture, foci were observed in erionite-exposed cells but not in glass beads-treated cells. (i) HM; (ii) HM cocultured with macrophages; (iii–vi) HM cocultured with macrophages and exposed to (iii) glass beads, (iv) US erionite from ND, (v) US erionite from Oregon, and (vi) Turkey erionite. (B) After 2 mo in culture, the numbers of tridimensional foci formed in HM cells under different treatment conditions were counted. Treatments were done in triplicates. OR, Oregon; TUR, Turkey. *P < 0.05 and ***P < 0.0001 compared with glass beads using unpaired t test. (C) Western blot analyses show that exposure to erionite fibers induced the release of HMGB1 by HM and TNF-α by macrophages. In the untreated negative control (lane 1) or cells treated with glass beads (lane 2), HMGB1 is mostly retained intracellularly (IC). HMGB1 was released from the HM cells into the conditioned medium (CM) as the cells underwent programmed necrosis, which is induced by exposure to US erionite from ND (lane 3), US erionite from Oregon (lane 4), or Turkey erionite (lane 5). Crocidolite asbestos (lane 6) was used as a positive control. Macrophages produced and secreted TNF-α into the conditioned medium 48 h after being exposed to the erionite fibers. (D) Immunohistochemical analyses show HMGB1 staining around areas of inflammation caused by crocidolite and erionite deposits. At low magnification (100×) H&E staining shows areas of the greater omentum from the peritoneum of mice injected with ASB or ND erionite or TUR erionite. Analysis at higher magnification (400×) shows adipose tissues with asbestos and erionite fibers surrounded by inflammatory cells, macrophages, giant cells, and lymphocytes. On the same samples, HMGB1 is detected in both cytoplasm and extracellular space where F4/80 and wide spectrum cytokeratin antibodies identify macrophages and mesothelial cells, respectively.