In vitro correlates of mineral dust toxicity

Our plain-English summary of In vitro correlates of mineral dust toxicity, by R.C. Brown, A. Poole, C.J. Turver (Food and Chemical Toxicology, 1986).

The study

• Authors: R.C. Brown, A. Poole, C.J. Turver
• Journal: Food and Chemical Toxicology
• Published: 1986;24(6-7):535-8
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In vitro studies of mineral fibres have shown that these materials are capable of causing the production of free radical damage (measured by the accumulation of thiobarbituric acid-reactive material) in a way that does not depend on fibre morphology but rather on a surface property, probably the presence of iron. The DNA-damaging activities of the same dusts were measured in an assay based on the production of single-stranded DNA. Activity in this assay was again not dependent on the presence of fibres. In contrast the cytotoxicity of mineral fibres towards V79-4 cells correlated better with in vivo tumorigenicity than did either of the above activities. The activity of fibres against a macrophage-like cell demonstrated that both fibre morphology and chemical properties are important determinants of biological activity.

In plain English

This was a laboratory study. The authors exposed cultured cells to mineral dusts to see whether fibre size or surface chemistry drove different effects. They tested UICC crocidolite and amosite, versions of these milled into non-fibrous dust, a glass fibre, and silanized (surface-treated) versions.

In A549 cells, crocidolite raised a marker of free-radical damage (malondialdehyde) after 24 hours. Crocidolite and amosite raised it whether intact or milled, and the milled samples raised it more. Glass fibre had no effect, and silanization brought levels near control.

In macrophage-like P388D1 cells, silanization reduced the effect of glass fibre but not of crocidolite. Silanized glass fibre was about as toxic to V79-4 Chinese hamster cells as the untreated fibre. Milling did not change crocidolite's damaging effect on DNA.

The authors compared these results with earlier published rat injection results. They judged that toxicity to V79 cells matched tumour-forming activity better than DNA damage or the free-radical marker did. The authors concluded that both size and chemistry determine the biological effects of mineral fibres.

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 experiments
• Who was studied: Cultured cell lines: A549 cells (free-radical marker), P388D1 macrophage-like cells (arachidonic acid release) and V79-4 Chinese hamster cells (cytotoxicity). The DNA damage experiment does not state which cell line was used. A C3H10T1/2 line is listed in the methods, but no results are reported for it.
• Exposure: Dusts tested:
• UICC crocidolite and amosite asbestos
• crocidolite and amosite ball-milled for 8 hours
• a respirable fraction of Johns-Manville code 100 glass fibre
• silanized (derivatized) versions of these fibres

Doses used:

• 20 to 50 micrograms per square centimetre for the free-radical marker
• 40 to 320 micrograms per ml for arachidonic acid release
• 2.5 to 20 micrograms per ml for V79-4 toxicity
• 100 to 400 for the DNA assay
• Main results:
  • In A549 cells, crocidolite had little effect at 2.5 hours. At 24 hours, every dose significantly increased malondialdehyde: control 0.12 nmol per culture, compared with 1.44 at 20, 1.87 at 40 and 1.94 at 50 micrograms per square centimetre.
  • At 50 micrograms per square centimetre in A549 cells, malondialdehyde (nmol per culture) was:
• control: 2.37
• crocidolite: 3.46
• milled crocidolite: 4.45
• amosite: 3.46
• milled amosite: 4.06
• glass fibre: 2.42

The milled samples were more active.

• Silanization lowered malondialdehyde to near control levels: 2.82 for silanized crocidolite and 2.60 for silanized amosite. Both were significantly different from the untreated dust at the 5% level.
• In P388D1 macrophage-like cells at 320 micrograms per ml, arachidonic acid release (as % of control) was:
• glass fibre: 451 untreated, 282 silanized
• crocidolite: 295 untreated, 301 silanized
  • Silanized glass fibre was about as toxic to V79-4 cells as the untreated glass fibre. For example, cell survival at 10 micrograms per ml was 23% of control for untreated fibre and 10% for silanized fibre.
  • Loss of nitrocellulose-bound DNA (a measure of DNA damage):
• controls: 10.3% (20 determinations)
• UICC crocidolite: 54.0%, 50.9% and 62.9% at 100, 200 and 400
• milled crocidolite: 46.9%, 66.6% and 64.5% at the same doses

The crocidolite figures are each from 3 determinations.

• The authors' conclusion: The authors concluded that the biological effects of mineral fibres are determined by both their size and their chemistry, and that the results depend on the fibre and the test system. They compared their results with an earlier rat intrapleural injection study by other researchers, in which milled crocidolite was less active than UICC crocidolite. On that basis they judged that cytotoxicity agreed better with the in vivo response than DNA damage or malondialdehyde accumulation did.
• Limitations the authors state:
  • The authors stated that, once fibres are in the lung, clearance, dissolution and coating change their size and surface chemistry. They said these effects cannot yet be adequately predicted, so short-term tests (in vivo or in vitro) of new fibres remain problematic.
  • The authors described the DNA damage measure as only roughly proportional to the original damage.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage.

Related studies

• Cytotoxic action of mineral dusts on CHV 79 cells in vitro: factors affecting toxicity — S.O. Lock, M. Chamberlain (1983)
• Stimulation of alveolar macrophages by mineral dusts in vitro: luminol-dependent chemiluminescence study — V. Vilím, J. Wilhelm, et al. (1987)
• Effect of mineral dusts on metabolic cooperation between Chinese hamster V79 cells in vitro — M. Chamberlain (1983)
• Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles — Y. Oghiso, Y. Kubota (1987)
• Polyvinylpyridine-N-oxide and carboxymethyl cellulose inhibit mineral dust-induced production of reactive oxygen species by human macrophages — P. Nyberg (1991)
• Reaction of mineral dusts with primary lung fibroblast cultures — R.J. Richards, J. Hunt (1983)

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