Erionite and asbestos differently cause transformation of human mesothelial cells

Our plain-English summary of Erionite and asbestos differently cause transformation of human mesothelial cells, by P. Bertino, A. Marconi, L. Palumbo, et al (International Journal of Cancer, 2007).

The study

• Authors: P. Bertino, A. Marconi, L. Palumbo, B.M. Bruni, D. Barbone, S. Germano, A.U. Dogan, G.F. Tassi, C. Porta, L. Mutti, G. Gaudino
• Journal: International Journal of Cancer
• Published: 2007;121(1):12-20
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.

In plain English

This laboratory (in vitro) study compared how erionite and asbestos fibers affect human mesothelial cells (HMC). Two primary HMC cultures from patients with heart failure were exposed, without SV40 infection, to erionite from Karain (Turkey) and Oregon (USA), UICC amosite, UICC chrysotile B, or glass fibers, short-term (24 hours, 0.1–10 micrograms per square centimetre) and long-term (two 72-hour cycles at 2.5 micrograms per square centimetre, followed for two months). Scanning electron microscopy of the erionite samples found 26.0% (Karain) and 30.1% (Oregon) of fibers in the size category suggested as most carcinogenic in rats. Calculations put the dust in the size range considered more biologically active at 19 and 180 fibers per microgram for the two erionites, against about 1.5 x 10^5 (chrysotile) and 1.2 x 10^5 (amosite), whose sizes came from earlier transmission electron microscopy data. Erionite was less cytotoxic than amosite, produced more 8-OHdG DNA adducts, and gave more Ki67-positive cells (Karain 6.2%, Oregon 5.0%) than amosite (2.6%) or glass (2.1%). Only erionite produced foci; none arose from 3 x 10^5 cells exposed to amosite, chrysotile or glass. The authors concluded erionite can transform HMC by itself.

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: in vitro cell-culture experiment comparing fiber types, with scanning electron microscopy characterisation of the erionite samples
• Who was studied: Two primary human mesothelial cell (HMC) cultures obtained from patients with heart failure; laboratory study (Italy)
• Exposure: Erionite fibers from Karain (Turkey) and Oregon (USA), UICC amosite, UICC chrysotile B and glass fibers; short-term 24 hours at 0.1-10 micrograms per square centimetre, long-term two 72-hour cycles at 2.5 micrograms per square centimetre
• Main results:
  • In the erionite samples examined by scanning electron microscopy, fibers in the dimensional category suggested as having the highest carcinogenic potential in rats made up 26.0% of the Karain and 30.1% of the Oregon samples
  • The size distributions of the UICC asbestos samples were not measured in this study but taken from previous transmission electron microscopy data
  • Calculations from the size distributions put the dust in the size range considered more biologically active at 19 fibers per microgram for Karain erionite and 180 for Oregon erionite, versus about 1.5 x 10^5 for UICC chrysotile and 1.2 x 10^5 for UICC amosite
  • At 24 hours, erionite caused dose-dependent cytotoxicity in HMC far lower than amosite, statistically significant at 5 and 10 micrograms per square centimetre (p value printed as 0.001, inequality sign lost in the text); chrysotile was comparable to erionite and glass fibers showed no detectable cytotoxicity
  • Nuclear fragmentation (Hoechst staining) in HMC: VP16 11.3%, amosite 12.4%, Karain erionite 3.9%, Oregon erionite 5.6%, glass beads 2.5%; differences reported as statistically significant
  • 8-OHdG DNA adducts were significantly induced by amosite and erionite compared with unexposed controls or glass, with erionite producing far more adducts than amosite; adducts fell significantly when the antioxidant N-Acetyl-L-Cysteine was present
  • Ki67-positive HMC after 24 hours: Karain erionite 6.2%, Oregon erionite 5.0%, amosite 2.6%, glass 2.1%, untreated 3.2%; erionite differences reported as statistically significant
  • After long-term exposure, foci formed only with erionite: frequency 1.0 x 10^-4 (SD 0.65 x 10^-4) for Karain and 0.3 x 10^-4 (SD 0.46 x 10^-4) for Oregon; no foci developed from 3 x 10^5 cells exposed to glass, amosite or chrysotile
  • Cells derived from erionite-induced foci showed higher expression of HGFR/Met, EGFR and PDGFR-beta and higher Akt, Erk1/2 and NF-kappaB activity than untransformed HMC
• The authors' conclusion: The authors concluded that erionite has intrinsic transforming properties and can transform human mesothelial cells by itself, without SV40, and that exposure to low concentrations of such fibers warrants careful hazard evaluation
• Limitations the authors state:
  • The authors state they could not prepare an adequately fiber-enriched erionite sample, because erionite in Karain is a minor constituent of a volcanic rock
  • The authors state they cannot exclude that components of the non-fibrous material in the erionite samples potentiated the effect of the fibrous fraction
  • The authors state that genetic predisposition to the effect of erionite was not addressed here and is a separate subject for investigation
  • Supporting data on rescue of sensitivity with PI3K and NF-kappaB inhibitors are not presented in the article

Topics

Medical terms in this study, explained in our Lexicon: erionite, Mesothelial Cells, Malignant Mesothelioma, Occupational Exposure, Zeolite, Carcinogenic, SV40, Environmental Exposure.

Related studies

• Continuous exposure to chrysotile asbestos can cause transformation of human mesothelial cells via HMGB1 and TNF-α signaling — F. Qi, G. Okimoto, et al. (2013)
• Patterns of c-fos and c-jun proto-oncogene expression, apoptosis, and proliferation in rat pleural mesothelial cells exposed to erionite or asbestos fibers — C.R. Timblin, G.D. Guthrie, et al. (1998)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)
• Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy — J. Xue, S. Patergnani, et al. (2020)
• Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma — M. Carbone, H. Yang (2012)
• BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation — A. Bononi, C. Giorgi, et al. (2017)

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