In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos

Our plain-English summary of In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos, by C. Varga, G. Horváth, V. Timbrell (Cancer Letters, 1996).

The study

• Authors: C. Varga, G. Horváth, V. Timbrell
• Journal: Cancer Letters
• Published: 1996;105(2):181-5
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Early cytogenetic action of oral exposure to UICC anthophyllite, an amphibole type of asbestos, was studied in Fischer-344 rats. The animals were gavaged with a suspension of untreated fibres (50 mg/kg) and fibres which had been allowed to adsorb benzo[alpha]pyrene molecules from aqueous solutions of 0.25-2.5 micrograms/ml. HPLC measurements indicated effective adsorption of the benzo[alpha]pyrene molecules on the fibres. The authors consider this system a suitable model for the drinking of water containing asbestos fibres and organic micropollutants. The formation of micronuclei and sister chromatid exchanges was studied in bone marrow samples taken from animals 24 h after oral administration of suspensions. Whereas anthophyllite fibres failed to induce cytogenetic alterations, fibres pretreated with the polycyclic aromatic solutions caused dose-dependent increase in the sister chromatid exchange frequencies. The observed cytogenetic impact can be explained by a local action of carcinogen molecules accumulated and subsequently transported. The results support the hypothesis that epidemiological evidence of carcinogenicity of asbestos in potable water may rather be explained by cogenotoxic action of the asbestos fibres and biologically active organic micropollutants adsorbed on their surface.

In plain English

This was an animal experiment in young female Fischer-344 rats. The authors gave rats a single stomach-tube dose (50 mg/kg body weight) of UICC anthophyllite asbestos, an amphibole type. The fibres were either untreated or had first been shaken in water containing benzo[a]pyrene (BaP), a cancer-causing chemical, at 0.25 to 2.50 micrograms per millilitre. Bone marrow was examined 24 to 26 hours later for two signs of chromosome damage, micronuclei and sister chromatid exchanges (SCEs), in three rats per exposed group; the micronucleus test had six untreated controls. The solutions lost all their BaP during shaking. Untreated fibres did not raise SCE frequency, and the micronucleus test showed no dose-related change. With BaP-coated fibres, SCEs rose from 1.96 per cell in untreated controls to 2.82, 2.90 and 3.17 in the 0.50, 1.00 and 2.50 groups. Each of these was statistically significant against controls. The authors concluded that the coated fibres showed early cogenotoxic action. They noted bone marrow is not thought to be a real asbestos target, and called for studies of tissues such as intestinal lining.

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: animal experiment (in vivo cytogenetic study in rats given asbestos by stomach tube)
• Who was studied: Young female Fischer (F-344) inbred rats. Micronucleus test: 3 rats in each of 5 exposed groups (A to E), about 200 g each, plus 6 untreated control rats (group K). SCE test: 3 rats per group, about 100 g each. Location: Debrecen, Hungary (the authors' institutions). Dates not stated.
• Exposure: A single oral gavage of UICC anthophyllite asbestos (from the Paakkila mine, Finland) at 50 mg/kg body weight. Group A received untreated fibres shaken in distilled water. Groups B to E received fibres that had been shaken overnight in benzo[a]pyrene solutions of 0.25, 0.50, 1.00 and 2.50 micrograms per millilitre, then rinsed. Group K was an untreated control group.
• Main results:
  • Chemical (HPLC) analysis showed complete loss of benzo[a]pyrene from the water solutions after overnight shaking with the anthophyllite fibres.
  • In the authors' comparison with UICC crocidolite, the anthophyllite fibres showed greater adsorptive activity for benzo[a]pyrene.
  • No toxic effect on blood-cell formation, and no mitotic inhibition or considerable delay, was seen in the bone marrow of treated rats.
  • The micronucleus test showed no dose-dependent change in genotoxic activity for fibres, whether treated or untreated.
  • Untreated anthophyllite fibres (group A) did not enhance the SCE frequency: 2.45 SCEs per cell (SD 0.74), against 1.96 (SD 0.32) in untreated controls (group K).
  • Fibres coated with benzo[a]pyrene raised SCE frequency compared with the untreated control average. The differences were statistically significant in the 0.50 to 2.50 microgram per millilitre groups: 2.82 SCEs per cell (SD 0.16, p less than 0.02) at 0.50; 2.90 (SD 0.38, p less than 0.05) at 1.00; and 3.17 (SD 0.28, p less than 0.01) at 2.50. The 0.25 group had 2.45 (SD 0.57), which was not marked as significant.
• The authors' conclusion: The authors concluded that UICC anthophyllite showed a high capacity to adsorb benzo[a]pyrene from water, and that the coated fibres showed early cytogenetic (cogenotoxic) action in orally exposed rats. They stated that the results support the idea that links between asbestos in drinking water and cancer may be explained by the combined action of fibres and organic pollutants adsorbed on them.
• Limitations the authors state:
  • Bone marrow is not thought to be a real target for asbestos. The authors said studies on relevant tissues such as intestinal lining, omentum and peritoneum would be needed to understand the mechanism and the real health risk.
  • The micronucleus test had wide standard deviations and poor reproducibility, which the authors said made it of no practical value for this purpose.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Paakkila mine, Finland

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Genotoxicity, UICC, Anthophyllite, Amphibole Group, Micronuclei.

Related studies

• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats — C. Varga, G. Horváth, et al. (1998)
• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay — C. Varga, G. Horváth, et al. (1999)
• Genotoxicity of dimethylnitrosamine in the presence of chrysotile asbestos UICC B and xonotlite — F. Denizeau, M. Marion, et al. (1985)
• Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo — P.M. Cook, L.D. Palekar, et al. (1982)
• Carcinogenic implications of the lack of tremolite in UICC reference chrysotile — A.L. Frank, R.F. Dodson, et al. (1998)
• Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis — D. Aierken, Y. Okazaki, et al. (2014)

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