Investigating palygorskite's role in the development of mesothelioma in southern Nevada: Insights into fiber-induced carcinogenicity

Our plain-English summary of Investigating palygorskite's role in the development of mesothelioma in southern Nevada: Insights into fiber-induced carcinogenicity, by D. Larson, A. Powers, J.P. Ambrosi, et al (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2016).

The study

• Authors: D. Larson, A. Powers, J.P. Ambrosi, M. Tanji, A. Napolitano, E.G. Flores, F. Baumann, L. Pellegrini, C.J. Jennings, B.J. Buck, B.T. McLaurin, D. Merkler, C. Robinson, P. Morris, M. Dogan, A.U. Dogan, H.I. Pass, S. Pastorino, M. Carbone, H. Yang
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2016;19(5-6):213-230
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Similar to asbestos fibers, nonregulated mineral fibers can cause malignant mesothelioma (MM). Recently, increased proportions of women and young individuals with MM were identified in southern Nevada, suggesting that environmental exposure to carcinogenic fibers was causing the development of MM. Palygorskite, a fibrous silicate mineral with a history of possible carcinogenicity, is abundant in southern Nevada. In this study, our aim was to determine whether palygorskite was contributing to the development of MM in southern Nevada. While palygorskite, in vitro, displayed some cytotoxicity toward primary human mesothelial (HM) cells and reduced their viability, the effects were roughly half of those observed when using similar amounts of crocidolite asbestos. No Balb/c (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16 Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM development was associated with a decreased acute inflammatory response, as injection of palygorskite resulted in lower percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to injection of crocidolite. Additionally, compared to mice injected with crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor-promoting) macrophages (p = .008) in their peritoneal cavities when exposed to fiber for several weeks. Our study indicates that palygorskite found in the environment in southern Nevada does not cause MM in mice, seemingly because palygorskite, in vivo, fails to elicit inflammation that is associated with MM development. Therefore, palygorskite is not a likely contributor to the MM cases observed in southern Nevada.

In plain English

This laboratory study tested whether palygorskite, a fibrous mineral common in southern Nevada soils, could cause malignant mesothelioma (MM). The researchers examined palygorskite from four southern Nevada sites, but the cell and mouse experiments used a pure palygorskite standard from a clay repository. Crocidolite asbestos was the positive control and glass beads the negative control. In human mesothelial cells grown in the lab, palygorskite damaged cells and reduced their viability, but less than crocidolite. Depending on the test, 5.9 to 12.4 µg/cm2 of palygorskite matched the effect of 5 µg/cm2 of crocidolite. In mice injected in the abdominal (peritoneal) cavity, no Balb/c mice (0 of 19) or MexTAg mice (0 of 18) given palygorskite developed MM. By comparison, 3 of 16 Balb/c and 13 of 14 MexTAg mice given crocidolite did. Compared with crocidolite-injected mice, palygorskite-injected mice had lower percentages of inflammatory cells, a lower percentage of M2 (tumor-promoting) macrophages and no mesothelial hyperplasia. The authors concluded that palygorskite fibers found in southern Nevada are not carcinogenic. They noted that they cannot rule out that palygorskite with different physical characteristics might cause MM.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: in vitro tests on human mesothelial cells plus animal experiments with intraperitoneal fiber injection in mice; also collection and electron-microscope measurement of palygorskite samples from southern Nevada
• Who was studied: Primary human mesothelial cells from the pleural fluid of patients with nonmalignant ailments (from at least 2 patients). Balb/c mice and MexTAg transgenic mice, which the authors describe as much more susceptible to asbestos carcinogenesis. The long-term tumor experiment used 3 glass, 19 palygorskite and 16 crocidolite Balb/c mice, and 15 glass, 18 palygorskite and 14 crocidolite MexTAg mice. Palygorskite samples came from four sites in southern Nevada.
• Exposure: Pure palygorskite (Source Clays Repository standard) compared with crocidolite asbestos (positive control) and glass beads (negative control). In the tumor experiments, Balb/c mice received two 1 mg intraperitoneal injections 1 week apart. MexTAg mice received two injections 1 month apart: 6 mg of palygorskite or glass, or 3 mg of crocidolite. Separate Balb/c mice received repeated 0.5 mg injections over 5 weeks to look for hyperplasia and macrophage types.
• Main results:
  • In human mesothelial cells, palygorskite caused more cell damage than glass beads and reduced cell viability, with a dose effect, but was less cytotoxic than crocidolite.
  • The authors calculated how much palygorskite matched the effect of 5 µg/cm2 of crocidolite: 5.9 µg/cm2 (LDH assay), 11.7 µg/cm2 (Alamar blue assay) and 12.4 µg/cm2 (MTS assay).
  • Balb/c mice: MM in 0/19 given palygorskite, 0/3 given glass and 3/16 (18.8%) given crocidolite. Ascites occurred in 5/16 (31.3%) crocidolite mice and in none given palygorskite or glass.
  • MexTAg mice: MM in 0/18 given palygorskite, 0/15 given glass and 13/14 (92.9%) given crocidolite.
  • Three days after injection, crocidolite-injected mice had higher percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity than palygorskite-injected mice.
  • After repeated injections over 5 weeks, no mesothelial hyperplasia was found in palygorskite- or glass-exposed mice. It was always observed in crocidolite-injected mice.
  • After sustained exposure, crocidolite-injected mice had higher percentages of M2 macrophages than mice injected with glass (p = .008) or with palygorskite (p = .008).
• The authors' conclusion: The authors concluded that palygorskite mineral fibers found in southern Nevada are not carcinogenic, presumably because they elicit much less inflammation than crocidolite.
• Limitations the authors state:
  • The authors cannot completely rule out that palygorskite with different physical characteristics exists and may cause MM.
  • The authors did not test the fibers on mouse mesothelial cells in vitro.
  • Because palygorskite was difficult to purify from the environmental samples, the cell and mouse experiments used a pure commercial standard rather than the Nevada samples. The authors reported that the standard's fiber dimensions were nearly identical to those of the Nevada samples.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Palygorskite (Attapulgite), Mesothelioma, Mineral Fiber, Environmental Exposure, Carcinogenic, Silicate, Crocidolite, Macrophage.

Related studies

• Characterisation of palygorskite specimens from different geological locales for health hazard evaluation — R.P. Nolan, A.M. Langer, et al. (1991)
• The Presence of Asbestos in the Natural Environment is Likely Related to Mesothelioma in Young Individuals and Women from Southern Nevada — F. Baumann, B.J. Buck, et al. (2015)
• Cytotoxicity of respirable dusts from industrial minerals: comparison of two naturally occurring and two man-made silicates — D. Nadeau, L. Fouquette-Couture, et al. (1987)
• Rat lung reactivity to natural and man-made fibrous silicates following short-term exposure — I. Lemaire, P.G. Dionne, et al. (1989)
• Sister chromatid exchanges in rat pleural mesothelial cells treated with crocidolite, attapulgite, or benzo 3-4 pyrene — S. Achard, M. Perderiset, et al. (1987)
• A retrospective cohort mortality study of males mining and milling attapulgite clay — R.J. Waxweiler, R.D. Zumwalde, et al. (1988)

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