Long and short fiber amosite asbestos alters at a different extent the redox metabolism in human lung epithelial cells

Our plain-English summary of Long and short fiber amosite asbestos alters at a different extent the redox metabolism in human lung epithelial cells, by C. Riganti, E. Aldieri, L. Bergandi, et al (Toxicology and Applied Pharmacology, 2003).

The study

• Authors: C. Riganti, E. Aldieri, L. Bergandi, M. Tomatis, I. Fenoglio, C. Costamagna, B. Fubini, A. Bosia, D. Ghigo
• Journal: Toxicology and Applied Pharmacology
• Published: 2003;193(1):106-15
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The mechanism by which asbestos fibers are fibrogenic and tumorigenic is still matter of debate. The higher pathogenicity of longer fibers has been traditionally associated with their slower clearance in respiratory airways. However, short amosite fibers, obtained by grinding longer ones, exhibited a lower potential to damage nude DNA and a lower in vitro cytotoxicity. We have thus revisited the two sets of long and short fibers in order to compare their surface properties to their activity in cell systems. In this study we report that, in human lung epithelial cells A549, long amosite fibers, more effectively than the short ones, initiate free radical reactions, inhibit the glucose 6-phosphate dehydrogenase activity and the pentose phosphate pathway, decrease the intracellular level of reduced glutathione, and increase the generation of thiobarbituric acid reactive substances and the leakage of lactate dehydrogenase in the extracellular medium. These results suggest that the shortening of fibers by prolonged milling affects not only their biopersistence, but also their surface properties, hence their interaction with cellular metabolism. Our data provide also a mechanism by which asbestos fibers inhibit the pentose phosphate pathway, i.e., via the oxidative inhibition of glucose 6-phosphate dehydrogenase, which is prevented by reduced glutathione.

In plain English

This was a laboratory study in cultured cells, not in people. The authors compared long amosite asbestos fibers with short fibers made by prolonged grinding of them, both from one South African batch. They exposed human lung epithelial cells (A549), and sometimes mouse glial cells (N11), to equal masses of each for 24 hours. Long fibers significantly reduced the activity of the pentose phosphate pathway, and of its key enzyme G6PD, at every concentration tested. Short fibers inhibited G6PD only at the highest concentration, and less efficiently; at that concentration they reduced the pathway only when it was stimulated by the oxidant menadione. In the human cells, long fibers but not short ones lowered the protective substance reduced glutathione, raised a lipid-damage marker (TBARS), and caused cell damage measured as LDH leakage. In a cell-free test, long fibers generated much more free-radical activity, although the short-fiber sample had nearly twice the surface area per gram. The authors concluded that the differences came mostly from changes to the mineral caused by prolonged milling, not simply from fiber length.

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 cultured cells, plus cell-free tests on purified enzyme and fiber suspensions
• Who was studied: Human lung epithelial cell line A549, plus the N11 mouse glial cell line in some experiments; no human or animal subjects
• Exposure: Long fiber amosite (LFA) and short fiber amosite (SFA). Both came from the same batch of South African amosite supplied by the Institute of Occupational Medicine, Edinburgh. SFA was made by grinding LFA. Both were used at equal mass concentrations, mainly 35, 3.5 and 0.35 per square centimetre of culture dish (unit prefix lost in the text).
• Main results:
  • In A549 cells, every concentration of long fibers significantly inhibited both basal and menadione-stimulated pentose phosphate pathway activity.
  • In A549 cells, short fibers did not significantly inhibit pentose phosphate pathway activity except at the higher concentration. At that concentration they decreased only the menadione-stimulated pathway activity.
  • In A549 cells, long fibers significantly inhibited G6PD enzyme activity at each concentration. Short fibers were effective only at the higher dose and less efficiently.
  • The fall in G6PD activity was not due to reduced production of G6PD protein or mRNA.
  • With purified G6PD enzyme, long fibers inhibited activity by more than 60% versus control after 6 hours.
  • With purified G6PD enzyme, short fibers reduced activity significantly only at 6 hours.
  • Reduced glutathione (GSH) significantly reversed the inhibition of purified G6PD by long fibers.
  • In A549 cells, long fibers but not short fibers significantly decreased the ratio of reduced to oxidized glutathione inside the cells.
  • At concentration 3.5, long fibers raised the lipid peroxidation marker TBARS in A549 cells to about the same level as the oxidant menadione. Short fibers did not raise TBARS.
  • At concentration 3.5, long fibers caused a significant increase in LDH leakage, a measure of cell damage, from A549 cells. Short fibers produced no significant cytotoxic effect at either dose tested.
  • In N11 mouse glial cells, both long and short fibers significantly caused pathway inhibition, glutathione depletion and LDH leakage. Short fibers were less effective.
  • In N11 cells, adding GSH reversed the pathway inhibition and LDH release caused by both long and short fibers.
  • In the cell-free spin-trapping test, long fibers gave a much stronger free-radical signal than short fibers.
  • The authors measured a specific surface area of 11.2 square metres per gram for short fibers and 6 square metres per gram for long fibers.
• The authors' conclusion: The authors concluded that the differences between long and short amosite were not simply due to fiber length. In their view, the differences mostly came from changes to the mineral's crystal chemistry caused by prolonged milling.
• Limitations the authors state:
  • The short fibers were produced artificially by grinding the long fibers.
  • A549 cells did not take up glutathione or N-acetylcysteine, so a mouse glial cell line had to be used to test protection by glutathione inside cells.
  • How milling changes fiber surface composition and reactivity was not examined in this paper.

Topics

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

Medical terms in this study, explained in our Lexicon: Amosite, Fibrogenic, Glutathione (GSH), Lactate Dehydrogenase (LDH), biopersistence.

Related studies

• Crocidolite asbestos inhibits pentose phosphate oxidative pathway and glucose 6-phosphate dehydrogenase activity in human lung epithelial cells — C. Riganti, E. Aldieri, et al. (2002)
• High aspect ratio materials: role of surface chemistry vs. length in the historical "long and short amosite asbestos fibers" — M. Tomatis, F. Turci, et al. (2010)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 3: Depletion of antioxidant defenses — E. Gazzano, C. Riganti, et al. (2005)
• 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)
• Cigarette smoke increases amosite asbestos fiber binding to the surface of tracheal epithelial cells — A. Churg, J. Sun, et al. (1998)
• Efflux of reduced glutathione after exposure of human lung epithelial cells to crocidolite asbestos — S.A. Golladay, S.H. Park, et al. (1997)

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