Impact of biopersistent fibrous dusts on glycolysis, glutaminolysis and serine metabolism in A549 cells

Our plain-English summary of Impact of biopersistent fibrous dusts on glycolysis, glutaminolysis and serine metabolism in A549 cells, by S. Wache, S. Helmig, D. Walter, et al (Molecular Medicine Reports, 2017).

The study

• Authors: S. Wache, S. Helmig, D. Walter, J. Schneider, S. Mazurek
• Journal: Molecular Medicine Reports
• Published: 2017;16(6):9233-9241
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The conversion rates of different metabolic pathways summarized as a metabolic signature mirror the physiological functions and the general physiological status of a cell. The present study compared the impact of crocidolite and chrysotile asbestos, glass fibers and multi‑walled carbon nanotubes (MWCN) of two different lengths (1‑2 µm and 5‑15 µm) on the conversion rates in glycolysis, glutaminolysis and serine metabolism of A549 cells. The concentration tested was 1 µg/cm2 for all fibers. A concentration of 5 µg/cm2 was additionally used for chrysotile and crocidolite, and 25 µg/cm2 for glass fibers and MWCN. With respect to the inhibitory effect on cell proliferation and the extent of metabolic alterations, the present study revealed the following ranking among the fibers tested: Chrysotile>crocidolite>glass fibers>MWCN 5‑15 µm>MWCN 1‑2 µm. For the asbestos and glass fibers this ranking correlated best with the number of fibers. It appeared that the results observed for MWCN did not match this correlation. However, electron microscopy revealed an agglomeration of MWCN. The agglomeration decreased the toxicologically relevant number of fibers by forming larger particle‑like shapes and explained the smaller effects of MWCN 5‑15 µm and 1‑2 µm on cell proliferation and metabolism.

In plain English

A549 human lung adenocarcinoma cells in culture were exposed to chrysotile and crocidolite asbestos, insulation glass fibers, and multi-walled carbon nanotubes 1-2 or 5-15 micrometres long. All fibers were tested at 1 microgram per square centimetre for 24 hours. For 48 hours, glass fibers and nanotubes were tested at 25, asbestos at 5, since 25 of either asbestos was cytotoxic. The doses used did not affect cell viability. At the low dose, chrysotile and glass fibers each cut growth 12%, while both nanotube types increased it. At the high doses, growth fell 54% with chrysotile, 29% with crocidolite, 22% with glass fibers and 23% with longer nanotubes. Shorter nanotubes did not change growth at the high dose. Low doses did not significantly change glucose, glutamine or serine use. At high doses, chrysotile caused the largest metabolic changes. The authors ranked the effects: chrysotile, crocidolite, glass fibers, longer nanotubes, then shorter nanotubes. This ranking matched fiber numbers per milligram for asbestos and glass fibers, but not nanotubes. The authors concluded that nanotube clumping reduced the relevant fiber number, explaining their smaller effects.

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) cell culture experiment
• Who was studied: A549 human lung adenocarcinoma cells obtained from the European Collection of Authenticated Cell Cultures. Replicates were 14 control and 6 dust-treated wells per fiber at the low dose, and 6 control and 4 dust-treated wells per fiber at the high dose.
• Exposure: The fibers were UICC South African crocidolite asbestos, UICC Rhodesian chrysotile asbestos, glass fibers (man-made vitreous fibers) from commercial insulation glass wool, and multi-walled carbon nanotubes 1-2 micrometres and 5-15 micrometres long. All fibers were tested at 1 microgram per square centimetre for 24 hours. At 48 hours, asbestos was tested at 5 and glass fibers and nanotubes at 25 micrograms per square centimetre. The authors reported 800 million WHO fibers per mg for chrysotile, 130 million for crocidolite and 0.26 million for glass fibers.
• Main results:
  • For both asbestos types, 25 micrograms per square centimetre for 48 hours was cytotoxic. Chrysotile and crocidolite were therefore applied at 5 micrograms per square centimetre at the high dose.
  • For all dusts, neither the low nor the high dose used in the experiments affected cell viability.
  • At the low dose (1 microgram per square centimetre, 24 hours), only chrysotile and glass fibers significantly inhibited cell proliferation, by 12% compared with mock-treated controls.
  • At the low dose, the 1-2 micrometre nanotubes increased cell proliferation by 16% and the 5-15 micrometre nanotubes by 9%. Both increases were significant.
  • In chrysotile-treated cells, inhibition of cell proliferation rose to 54% at 5 micrograms per square centimetre for 48 hours.
  • Crocidolite had no effect at the low dose and decreased cell proliferation by 29% at 5 micrograms per square centimetre for 48 hours.
  • Growth inhibition by glass fibers increased from 12% at the low dose to 22% at the high dose.
  • At 25 micrograms per square centimetre for 48 hours, the 5-15 micrometre nanotubes inhibited cell proliferation by 23%. The 1-2 micrometre nanotubes had no effect on cell proliferation at this dose.
  • At the low dose, no fibrous dust significantly changed the conversion rates of glucose, lactate, pyruvate, glutamine, glutamate or serine.
  • At the high doses, chrysotile had the most marked effect on metabolic conversion rates. At 5 micrograms per square centimetre for 48 hours, glucose and glutamine consumption and pyruvate, lactate and glutamate production all increased significantly.
  • The other fibrous dusts also increased these conversion rates at the high doses, with smaller effects in this order: crocidolite, glass fibers, 5-15 micrometre nanotubes, 1-2 micrometre nanotubes.
  • In glass fiber-treated cells, the increase in serine uptake was among the highest of the fibers tested.
  • Combining effects on proliferation and metabolism, the fibers ranked in this order: chrysotile, crocidolite, glass fibers, 5-15 micrometre nanotubes, 1-2 micrometre nanotubes.
  • For asbestos and glass fibers, the ranking correlated best with fiber number: 800 million fibers per mg for chrysotile, 130 million for crocidolite and 0.26 million for glass fibers.
  • The nanotube results did not fit this trend. Nanotubes have more fibers per unit of mass, yet they had the smallest effects.
  • Scanning electron microscopy showed that both nanotube types strongly tended to form clumps (agglomerates) in fluid.
• The authors' conclusion: The authors concluded that the ranking of the fibers' effects on the cells' metabolic signature correlated best with the relevant number of fibers. Asbestos and glass fibers followed their fiber counts. For the nanotubes, the authors held that clumping reduced the functionally relevant number of fibers, which explained their smaller effects.
• Limitations the authors state:
  • The doses were not chosen to identify no-observed-adverse-effect or lowest-observed-adverse-effect levels for the fibers.
  • Concentrations above 25 micrograms per square centimetre were not used because they covered the cells in an impenetrable layer of dust.
  • The molecular mechanism behind the ranking was not established. The authors proposed further experiments to identify it.

Topics

Medical terms in this study, explained in our Lexicon: A549 Cells, Crocidolite, Chrysotile.

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