Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre parameters to the key characteristics of carcinogens: A comprehensive model inspiring asbestos-induced cancer prevention strategies

Our plain-English summary of Bridging the gap between toxicity and carcinogenicity of mineral fibres by connecting the fibre parameters to the key characteristics of carcinogens: A comprehensive model inspiring asbestos-induced cancer prevention strategies, by A.F. Gualtieri, E. Ferrari, L. Rigamonti, et al (Current Research in Toxicology, 2024).

The study

• Authors: A.F. Gualtieri, E. Ferrari, L. Rigamonti, B. Ruozi, S. Mirata, V. Almonti, M. Passalacqua, S. Vernazza, S. Di Valerio, G. Tossetta, S. Vaiasicca, A.D. Procopio, F. Fazioli, D. Marzioni, A. Pugnaloni, S. Scarfì
• Journal: Current Research in Toxicology
• Published: 2024;7:100202
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects in vivo leading to carcinogenesis.

Methods: In vitro toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite. The analysis of the in vitro data allowed us to assess the major fibre parameters responsible for alterations in the key characteristics of carcinogens for each investigated fibre and the intensity of their effect.

Results: Crystal habit and density of the fibres affect exposure but are not major parameters contributing to the KCs. For chrysotile, besides length, we found that fibre parameters that greatly contribute to the KCs are the surface area and the dissolution rate with the related velocity of release of metals (namely iron). For crocidolite, they are the fibre length, iron content and related parameters like the ferrous iron content, iron nuclearity, transition metals content and zeta potential.

Conclusions: The results of our study can be a starting point for developing personalized cancer screening and prevention strategies as long as the nature of the fibre of the exposed patient is known. We can speculate on a future personalized prevention therapy targeting the fibres with surface-engineered nanocarriers with active complexes that are selective for the surface charge of the fibres. For chrysotile, a complex with deferasirox that can chelate Fe2+ and deferoxamine that preferentially chelates Fe3+ is proposed with the anchorage to the silica chrysotile surface driven by aspartic acid. For crocidolite, deferiprone chelating both Fe3+ and Fe2+ combined with lysine to attract the silica crocidolite surface is proposed.

© 2024 The Author(s).

In plain English

This was a laboratory study in human cells, not a study of people. The authors tested a commercial Russian chrysotile split into short (5 micrometres or less) and long (over 5 micrometres) batches, UICC crocidolite as the carcinogenic standard, and wollastonite as the non-carcinogenic standard. They ran cell tests for nine of the ten IARC 'key characteristics of carcinogens' (immortalization was not tested) and fed the results into their fibre-parameter model. Combined scores were 4.518 for wollastonite, 5.401 for short chrysotile, 6.988 for long chrysotile and 7.524 for crocidolite. The differences between the groups were not statistically significant (p = 0.073). The authors noted that, under IARC protocols, even wollastonite gave strong mechanistic evidence of carcinogenicity, so care is needed in interpretation. Apart from fibre length in the long batch, the model linked chrysotile's activity mainly to surface area, dissolution rate and release of iron and other metals. It linked crocidolite's activity to fibre length, iron and metal content and zeta potential. The authors concluded this could be a starting point for personalized prevention strategies, and they called their proposed iron-chelating treatment model speculative.

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 laboratory study (human cell lines) with results applied to the authors' fibre-parameter (FPTI) model
• Who was studied: Four fibre samples: short and long batches of a commercial chrysotile from the Ural Mountains (Russia), UICC crocidolite (South Africa), and wollastonite NYAD G (New York, USA). They were tested on the human cell lines MeT5A (mesothelial), HECV (endothelial), MRC-5 (lung fibroblast), A549 (lung adenocarcinoma) and THP-1 (monocyte-derived macrophages).
• Exposure: Cells were exposed to chrysotile (short and long fibres), crocidolite or wollastonite. Short-term experiments (up to 72 hours) used 50 micrograms per mL. Long-term experiments (7 to 21 days) used 10 or 25 micrograms per mL.
• Main results:
  • Sum of the normalized in vitro contributions across the key characteristics: wollastonite 4.518, short chrysotile 5.401, long chrysotile 6.988, crocidolite 7.524.
  • The Kruskal-Wallis test found the difference between the four fibre groups not statistically significant (chi-squared 6.97 with 3 degrees of freedom, p = 0.073).
  • For crocidolite, all tested key characteristics except KC 4 (epigenetic alterations) were active.
  • Crystal habit and fibre density did not contribute to the key characteristics in the model.
  • For chrysotile, fibre length was relevant for the long-fibre batch. The other main contributing parameters were surface area, dissolution rate, velocity of iron release and velocity of release of metals.
  • For crocidolite, the main contributing parameters were fibre length, iron content, ferrous iron content, iron nuclearity, content of other metals and zeta potential.
• The authors' conclusion: The authors concluded that their results can be a starting point for personalized cancer prevention strategies when the type of fibre a patient was exposed to is known. They described their proposed fibre-selective iron-chelating nanocarrier therapy as only a speculative model at present.
• Limitations the authors state:
  • Key characteristic 9 (immortalization) was not tested, because no literature data link fibre parameters to it.
  • The data were widely scattered, giving large standard deviations and variances.
  • Under IARC protocols the results would indicate strong mechanistic evidence of carcinogenicity even for the non-carcinogenic wollastonite, so the authors cautioned against treating these parameters as absolute measures of carcinogenicity.
  • The proposed prevention therapy is speculative and needs further modelling work.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, IARC, Chrysotile, UICC, Crocidolite, Wollastonite, Habit.

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