Reaction of mineral dusts with primary lung fibroblast cultures

Our plain-English summary of Reaction of mineral dusts with primary lung fibroblast cultures, by R.J. Richards, J. Hunt (Environmental Health Perspectives, 1983).

The study

• Authors: R.J. Richards, J. Hunt
• Journal: Environmental Health Perspectives
• Published: 1983;51:61-5
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The complex metabolism of rabbit lung fibroblast cultures maintained over 24 days in vitro and their interaction with the fibrogenic group of asbestos minerals is reviewed. The differential effects of nine dusts given as a single dose to 3-day-old fibroblast cultures which were then analyzed for DNA, protein and cell mat hydroxyproline after 3 weeks are discussed. A comparison is made of the ability of these minerals to promote reticulin deposition in vivo following instillation into rats with the ability of each mineral to alter cell mat hydroxyproline levels in fibroblast cultures. Because this comparison is poor for some of the minerals investigated, it is concluded that with the current methodology the fibroblast cultures do not provide an adequate in vitro test system for assessing the potential fibrogenicity of a mineral in vivo.

In plain English

This laboratory study, which also reviewed the authors' earlier work, tested nine mineral dusts on rabbit lung fibroblast cultures (collagen-making cells). Single doses of 10 to 1000 µg per culture were added on day 3. DNA and cell-layer collagen (hydroxyproline) were measured three weeks later. The dusts included UICC chrysotile asbestos, calcium silicates, two silicas, titanium dioxide, carbon and activated charcoal. Chrysotile, calcium silicate B and an "aged" calcium silicate lowered collagen as the dose rose. Titanium dioxide and A380 silica raised collagen at doses above 500 µg. Chrysotile was the only dust highly toxic to the fibroblasts. Low chrysotile doses (10 to 100 µg) may have slightly raised collagen; the authors said this needed confirmation. The authors compared these results with lung changes in rats given the dusts. The match was poor for some dusts, worst for the silicate samples, but agreed for DQ 12 quartz and A380 silica. The authors concluded that, with this method, fibroblast cultures were not yet an adequate test of a mineral's potential to cause fibrosis in living animals.

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 on lung fibroblast cultures, combined with a review of the authors' earlier work and a comparison with other in vitro tests and rat instillation results
• Who was studied: Primary rabbit lung fibroblast cultures, passages 4 to 6, with 3.5 to 4.0 x 10^5 cells seeded per bottle
• Exposure: Single doses of nine dusts (UICC chrysotile asbestos, calcium silicates A, B and 'aged', A380 silica, DQ 12 quartz, titanium dioxide, carbon, activated charcoal) at 10 to 1000 µg per culture, added on day 3, with DNA and cell mat hydroxyproline measured 3 weeks later
• Main results:
  • At 500 µg, all dust-treated cultures had higher DNA at day 7. Both calcium silicates usually kept this increase through the culture period; chrysotile did not.
  • Calcium silicate B, the 'aged' calcium silicate and chrysotile reduced cell mat hydroxyproline (collagen) in a dose-related way.
  • Cultures treated with A380 silica and titanium dioxide had raised hydroxyproline at doses above 500 µg.
  • Titanium dioxide was relatively inactive in vivo and in other in vitro tests, yet at 500 µg or more it raised hydroxyproline in fibroblast cultures.
  • DQ 12 quartz raised DNA in direct relation to dose, as did calcium silicate A up to 500 µg. Titanium dioxide and activated charcoal had little if any effect on DNA.
  • Chrysotile was the only mineral examined that was highly toxic to fibroblasts.
  • DQ 12 quartz and A380 silica produced alveolar wall thickening and excessive reticulin deposition in rats, with DQ 12 having the greater effect.
  • For DQ 12 quartz and A380 silica, the rat findings agreed with total lung hydroxyproline and with increases in DNA and hydroxyproline in fibroblast cultures.
  • The comparison between culture results and rat results was poor for some of the minerals, and the silicate samples showed the worst agreement.
  • Low doses of finely prepared chrysotile (10 to 100 µg) may have slightly raised hydroxyproline after 24 days; the authors said this needs confirmation.
• The authors' conclusion: The authors concluded that, using the methodology described, the fibroblast culture does not yet provide an adequate in vitro test system for assessing a mineral's potential fibrogenicity in vivo, because the comparison with rat results was poor for some minerals.
• Limitations the authors state:
  • The low-dose chrysotile finding requires confirmation.
  • Whether the dust-related rise in DNA reflects increased early cell growth was not established.
  • In earlier work, the response of fibroblasts to asbestiform minerals varied between cell strains, which raised doubts about the method.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibroblast, Fibrogenic, Asbestos, Deposition.

Related studies

• Biochemical effects of asbestiform minerals on lung fibroblast cultures — P.M. Hext, R.J. Richards (1976)
• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Ultrastructural changes in lung fibroblast cultures exposed to chrysotile asbestos — R.J. Richards, P.M. Hext, et al. (1974)
• The ability of mineral dusts and fibres to initiate lipid peroxidation. Part I: parameters which determine this ability — M. Gulumian (1999)
• The effects of long-term exposure of lung fibroblast strains to chrysotile asbestos — P.M. Hext, J. Hunt, et al. (1977)
• Pulmonary mineral dust. A study of ninety patients by electron microscopy, electron microanalysis, and electron microdiffraction — J.P. Berry, P. Henoc, et al. (1976)

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