Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells

Our plain-English summary of Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells, by R. Okayasu, L. Wu, T.K. Hei (British Journal of Cancer, 1999).

The study

• Authors: R. Okayasu, L. Wu, T.K. Hei
• Journal: British Journal of Cancer
• Published: 1999;79(9-10):1319-24
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceramic (RCF-1) fibre were studied using the human-hamster hybrid A(L) cells. Results from these fibres were compared with those of UICC Rhodesian chrysotile fibres. The A(L) cell mutation assay, based on the S1 gene marker located on human chromosome 11, the only human chromosome contained in the hybrid cell, has been shown to be more sensitive than conventional assays in detecting deletion mutations. Tremolite, erionite and RCF-1 fibres were significantly less cytotoxic to A(L) cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no significant mutant yield with any of these fibres. In contrast, both erionite and tremolite induced dose-dependent S1- mutations in fibre-exposed cells, with the former inducing a significantly higher mutant yield than the latter fibre type. On the other hand, RCF-1 fibres were largely non-mutagenic. At equitoxic doses (cell survival at approximately 0.7), erionite was found to be the most potent mutagen among the three fibres tested and at a level comparable to that of chrysotile fibres. These results indicate that RCF-1 fibres are non-genotoxic under the conditions used in the studies and suggest that the high mesothelioma incidence previously observed in hamster may either be a result of selective sensitivity of hamster pleura to fibre-induced chronic irritation or as a result of prolonged fibre treatment. Furthermore, the relatively high mutagenic potential for erionite is consistent with its documented carcinogenicity.

In plain English

This was a laboratory study on cells grown in dishes, not on people or animals. The authors exposed human-hamster hybrid cells (AL cells, which carry a single human chromosome, number 11) for 24 hours to three fibres: tremolite from Metsovo, Greece; erionite from Rome, Oregon, USA; and a man-made ceramic fibre, RCF-1. They compared the results with chrysotile results from the same laboratory's earlier work under identical conditions. All three fibres were significantly less toxic to the cells than chrysotile. The 'mean lethal dose' was about 4 micrograms per square centimetre for chrysotile, against 35 for RCF-1, 40 for tremolite and 42 for erionite. No fibre caused a significant rise in mutations at one gene (HPRT). At a second marker (S1), erionite and tremolite caused mutations that rose with dose, while RCF-1 showed no consistent dose response. At doses giving a cell survival fraction of about 0.7, erionite's mutation level was comparable to chrysotile's. Its mutant fraction was two- and tenfold higher than that of tremolite and RCF-1 respectively. The authors concluded that RCF-1 was non-genotoxic under their conditions and that erionite's mutagenic potential was consistent with its documented carcinogenicity.

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 cultured mammalian cells; new results for three fibres were compared with chrysotile data from the same laboratory's earlier study
• Who was studied: Human-hamster hybrid AL cells, which contain a full set of hamster chromosomes plus one copy of human chromosome 11, and a subclone of these cells (AHI-9). No people or animals were studied.
• Exposure: Tremolite (Metsovo, Greece), erionite (Rome, OR, USA) and RCF-1 man-made ceramic fibre (TIMA standard), compared with UICC Rhodesian chrysotile. Cells were treated for 24 h with graded doses (0 to 400 micrograms per millilitre, or 0 to 80 micrograms per square centimetre).
• Main results:
  • All three fibres were significantly less toxic to AL cells than chrysotile. The mean lethal dose was about 4 micrograms per square centimetre for chrysotile and 35, 40 and 42 for RCF-1, tremolite and erionite respectively.
  • RCF-1 was slightly more toxic than tremolite or erionite, but the differences were not statistically significant (P greater than 0.1).
  • At the HPRT gene, none of the three fibres induced a significant mutant yield at any dose tested.
  • At the S1 marker on human chromosome 11, erionite and tremolite produced mutations that increased with dose up to 20 micrograms per square centimetre.
  • For RCF-1 at the S1 marker, the difference in mutant fraction between the highest and lowest doses was not statistically significant (P greater than 0.5), and there was no consistent dose response.
  • Measured by fibre concentration, chrysotile was the most mutagenic of the fibres examined.
  • At doses giving a survival fraction of about 0.7 (2 micrograms per square centimetre for chrysotile, 10 for RCF-1, 20 for tremolite and erionite), erionite's mutagenic potential was comparable to chrysotile's. Its mutant fraction was two- and tenfold higher than that of tremolite and RCF-1 respectively.
  • RCF-1 fibres were substantially longer and wider than the chrysotile, tremolite and erionite fibres used.
• The authors' conclusion: The authors concluded that RCF-1 fibres were non-genotoxic under the conditions of the study, and that erionite's strong mutagenic potential was consistent with its carcinogenic effects reported in epidemiological and animal studies.
• Limitations the authors state:
  • The authors noted that toxicity measured in cell culture may have little or no relevance to the effects of mineral fibres in living bodies.
  • Cells were treated for only 24 hours, chosen so results matched the earlier chrysotile data. The authors stated that prolonged exposure to RCF-1 would be needed for mesothelioma to develop in animals.

Topics

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

Medical terms in this study, explained in our Lexicon: Tremolite, erionite, UICC, Chrysotile, Mesothelioma, Pleura.

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