Iron-loaded synthetic chrysotile: a new model solid for studying the role of iron in asbestos toxicity

Our plain-English summary of Iron-loaded synthetic chrysotile: a new model solid for studying the role of iron in asbestos toxicity, by E. Gazzano, F. Turci, E. Foresti, et al (Chemical Research in Toxicology, 2007).

The study

• Authors: E. Gazzano, F. Turci, E. Foresti, M.G. Putzu, E. Aldieri, F. Silvagno, I.G. Lesci, M. Tomatis, C. Riganti, C. Romano, B. Fubini, N. Roveri, D. Ghigo
• Journal: Chemical Research in Toxicology
• Published: 2007;20(3):380-7
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The generation of reactive oxygen species and other radicals, catalyzed by iron ions at the fiber surface, is thought to play an important role in asbestos-induced cytotoxicity and genotoxicity, but a direct confirmation of this statement needs the availability of asbestos samples differing only for their iron content, without the interference of other physicochemical features. Synthetic stoichiometric chrysotile nanofibers, devoid of iron or any other contaminant, did not exert genotoxic and cytotoxic effects nor elicited oxidative stress in a murine alveolar macrophage cell line; on the contrary, the same nanofibers, loaded with 0.57% and 0.94% (w/w) iron, induced DNA strand breaks, lipoperoxidation, inhibition of redox metabolism and alterations of cell integrity, similarly to natural chrysotile. On the other hand, the incubation with ferric nitrilotriacetate, a cell-permeating iron complex, even if it caused an intracellular overloading of iron very similar to that elicited by iron-loaded synthetic chrysotile and by natural chrysotile, did not exert any of these effects. This suggests that chrysotile is not toxic by acting simply as a carrier of iron into the cell, but rather that the redox activity of iron is potentiated when organized at the fibers surface into specific crystallographic sites having coordination states able to activate free radical generation. Synthetic chrysotile fibers may be proposed as a standard reference sample and model solids for experimental studies on asbestos fibers aiming to clarify the mechanisms of its toxicity and to synthesize new fibers devoid of pathogenic effects.

In plain English

This was a laboratory study in cultured cells, not people. The authors exposed a mouse lung immune-cell line (murine alveolar macrophages, MH-S) for 24 hours to natural chrysotile (UICC A), synthetic chrysotile nanofibers with no iron, the same synthetic fibers loaded with 0.57% or 0.94% iron by weight, or ferric nitrilotriacetate (FeNTA), an iron compound that enters cells. Iron-free synthetic fibers did not change measures of DNA damage. Natural chrysotile and both iron-loaded fibers significantly increased DNA strand breaks, leakage of the cell enzyme LDH and a lipid damage product. They also lowered the antioxidant glutathione and inhibited an antioxidant metabolic pathway. FeNTA at 1 micromolar raised cell iron to a level similar to that seen with natural chrysotile and with fibers loaded with 0.94% iron, but did not increase DNA damage. In cell-free tests with ascorbic acid, iron-loaded fibers produced carbon-centered radicals, while iron-free fibers and FeNTA did not. Without ascorbic acid, none were detected. The authors concluded that chrysotile is not toxic simply by carrying iron into cells. They said the low FeNTA concentrations were the likely reason it was not toxic.

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 (in vitro) experiment in a cultured cell line, plus cell-free tests of free radical generation
• Who was studied: MH-S murine (mouse) alveolar macrophage cell line, incubated for 24 hours with or without fibers
• Exposure: Synthetic stoichiometric chrysotile nanofibers either without iron or with controlled iron content (0.57% and 0.94% by weight), compared with natural UICC A chrysotile and with FeNTA (1 to 10 micromolar, alone or together with iron-free fibers)
• Main results:
  • In MH-S cells, all three comet-assay measures of DNA damage were significantly higher with UICC A chrysotile than in cells without fibers
  • DNA damage measures were not changed in cells incubated with iron-free synthetic chrysotile, but were significantly increased with synthetic chrysotile loaded with 0.57% and 0.94% iron
  • After 24 hours with 1 micromolar FeNTA, intracellular iron rose to a value very similar to that seen with UICC A chrysotile and with chrysotile loaded with 0.94% iron
  • 1 micromolar FeNTA caused no significant change in DNA damage measures compared with control, even when combined with iron-free chrysotile
  • With natural and iron-loaded chrysotile, intracellular glutathione (GSH) decreased in MH-S cells
  • With UICC A chrysotile and iron-loaded chrysotile, MH-S cells showed significant increases in LDH release (cytotoxicity) and MDA accumulation (lipid peroxidation)
  • Like natural chrysotile, iron-loaded synthetic fibers inhibited the pentose phosphate pathway (PPP) and the enzyme G6PD, without changing 6PGD activity
  • In cell-free tests, Fenton (hydroxyl radical) activity was absent with iron-free chrysotile but present for more than 1 hour with both FeNTA and iron-loaded fibers
  • Without ascorbic acid, no carbon-centered radicals were detected with any fiber type or with FeNTA
  • With ascorbic acid present, carbon-centered radicals were generated by iron-loaded synthetic chrysotile, already at the lowest iron content (0.57%), but not by iron-free chrysotile or FeNTA
• The authors' conclusion: The authors concluded that asbestos fibers are not toxic simply as iron carriers. They suggested that the fibers may increase iron's reactivity by holding iron ions in specific crystal sites at the fiber surface that can trigger free radical generation.
• Limitations the authors state:
  • The free radical (EPR) data were obtained under conditions necessarily different from those of the cell experiments
  • The authors stated that the much lower FeNTA concentrations used were the likely reason FeNTA did not itself cause toxicity

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Reactive Oxygen Species (ROS), Genotoxicity, Oxidative Stress, Alveolar Macrophage, Crystallographic Site.

Related studies

• Different cellular responses evoked by natural and stoichiometric synthetic chrysotile asbestos — E. Gazzano, E. Foresti, et al. (2005)
• The iron-related molecular toxicity mechanism of synthetic asbestos nanofibres: a model study for high-aspect-ratio nanoparticles — F. Turci, M. Tomatis, et al. (2011)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 2: Oxidant activity of the fibers — F. Turci, M. Tomatis, et al. (2005)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 3: Depletion of antioxidant defenses — E. Gazzano, C. Riganti, et al. (2005)
• Soil fungi reduce the iron content and the DNA damaging effects of asbestos fibers — S. Daghino, F. Turci, et al. (2006)
• The role of iron impurities in the toxic effects exerted by short multiwalled carbon nanotubes (MWCNT) in murine alveolar macrophages — E. Aldieri, I. Fenoglio, et al. (2013)

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