The in vitro activities of a highly carcinogenic mineral fibre--potassium octatitanate

Our plain-English summary of The in vitro activities of a highly carcinogenic mineral fibre--potassium octatitanate, by A. Poole, R.C. Brown, A.P. Rood (British Journal of Experimental Pathology, 1986).

The study

• Authors: A. Poole, R.C. Brown, A.P. Rood
• Journal: British Journal of Experimental Pathology
• Published: 1986;67(2):289-96
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

The in vitro activities of a highly carcinogenic potassium octatitanate fibre (Fybex) have been investigated. This material caused a low level of in vitro transformation in C3H10T1/2 cells and is thus more active in this assay than the UICC amphibole asbestos samples but less active than fibrous erionite. This ranking is in accord with carcinogenicity in vivo. However Fybex had no detectable activity in an assay for DNA damage based on the S1-nuclease sensitivity of the DNA from exposed cells. In that assay crocidolite asbestos was more active than either of the more carcinogenic dusts. It is suggested that the activities of amphibole asbestos in assays for genetic toxicity may depend on the production of free radicals via a catalytic reaction requiring the presence of transition elements which are either not present or only present at low concentrations in erionite or Fybex. This type of reaction may not be related to in vivo carcinogenicity. The action of fibrous dusts against macrophage-like cells, measured in this instance by the release of arachidonic acid, remains one of the best measures of biological activity.

In plain English

This laboratory study tested Fybex, a fibrous potassium octatitanate, on cultured mouse cells. The authors described the fibre as highly carcinogenic. Electron microprobe analysis showed it was pure potassium titanate. In a cell transformation test using C3H10T1/2 cells, Fybex was only weakly active. At 6.0 micrograms per millilitre, 1 of 12 flasks had transformed foci, and at 12.5 micrograms per millilitre, 2 of 12 did. There were none at 25 micrograms per millilitre and none in 16 control flasks. In a test for DNA damage, Fybex had no significant effect at any dose. At 250 micrograms per millilitre, crocidolite asbestos and erionite gave significant increases, while glass fibre and titanium dioxide did not. Fybex significantly increased arachidonic acid release from macrophage-like cells at 40 micrograms per millilitre and above. The authors concluded that, with present techniques, genotoxicity tests cannot rank mineral fibres by carcinogenicity, and that general cytotoxic activity remains the best predictor. They noted that the weak, poorly dose-related transformation response may indicate activity near the assay's detection limit. They also noted that the positive DNA damage results for other dusts came only at very high concentrations.

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 study: a cell transformation assay, a DNA damage assay based on S1 nuclease sensitivity, and an arachidonic acid release assay
• Who was studied: No people or animals. Two mouse cell lines were used: C3H10T1/2 cells (transformation and DNA damage assays) and the P388D1 murine macrophage-like cell line (arachidonic acid release assay)
• Exposure: Fybex (fibrous potassium octatitanate). Comparison dusts were UICC crocidolite asbestos, fibrous glass (JM100), Oregon erionite and titanium dioxide. Positive control chemicals were benzo(a)pyrene, NQO and TPA
• Main results:
  • The Fybex sample was pure potassium titanate. Of the fibres measured, 43.8% were under 0.2 micrometres in diameter and 50.5% were under 5 micrometres long
  • In C3H10T1/2 cells, Fybex caused low-level transformation. In Table 2, 1 of 12 flasks had type III foci at 6.0 micrograms per millilitre and 2 of 12 at 12.5 micrograms per millilitre. No foci were seen at 25 micrograms per millilitre, and 0 of 16 control flasks had foci
  • In the S1 nuclease DNA damage assay, no dose of Fybex (15 to 250 micrograms per millilitre) differed significantly from controls
  • In a separate S1 nuclease experiment with all dusts at 250 micrograms per millilitre, erionite (28.0) and crocidolite (34.2) released significantly more DNA than the control (15.8). Fybex (22.6), titanium dioxide (17.9) and JM100 glass fibre (21.0) did not
  • Fybex significantly increased arachidonic acid release from P388D1 cells. The mean was 2.54 in controls, 3.25 at 40 micrograms per millilitre and 7.18 at 320 micrograms per millilitre. Table 5 marks 40 micrograms per millilitre and above as significant
• The authors' conclusion: The authors concluded that, with present techniques, the genotoxic activities of mineral fibres cannot be used to rank them by carcinogenicity, and that general in vitro cytotoxic activity remains the best predictor of in vivo effect
• Limitations the authors state:
  • The small number of transformed foci and the poor dose-response may indicate that Fybex's activity was near the detection limit of the transformation assay
  • The authors judged the C3H10T1/2 transformation assay insufficiently sensitive for routine study of fibrous particles
  • The positive S1 nuclease results (for crocidolite and erionite, not Fybex) came only at dust concentrations far above those usable in the transformation studies. The authors judged their relevance to cancer in living animals debatable

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, UICC, Amphibole Asbestos, erionite, Crocidolite, Macrophage.

Related studies

• Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration — M. Abdelgied, A.M. El-Gazzar, et al. (2019)
• Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2018)
• In vitro genotoxic activities of fibrous erionite — A. Poole, R.C. Brown, et al. (1983)
• Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats — M. Yokohira, Y. Nakano-Narusawa, et al. (2016)
• Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity — M. Yokohira, Y. Nakano, et al. (2013)
• Histopathological changes in rat lung following intratracheal instillation of silicon carbide whiskers and potassium octatitanate whiskers — A. Ogami, Y. Morimoto, et al. (2007)

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