On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo\[a\]pyrene: II. Tissue specificity studies using comet assay

Our plain-English summary of On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay, by C. Varga, G. Horváth, V. Timbrell (Cancer Letters, 1999).

The study

• Authors: C. Varga, G. Horváth, V. Timbrell
• Journal: Cancer Letters
• Published: 1999;139(2):173-6
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epidemiological data seem to be equivocal on the probable increase in cancer incidence in populations exposed to asbestos-fibre contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of oral asbestos exposure, the large surface area of the fibres, however, creates the possibility of cogenotoxic action with adsorbed water-borne organics. In our animal model, rats were gavaged with untreated UICC crocidolite and anthophyllite fibres and fibres that had been allowed to adsorb benzo[a]pyrene molecules from aqueous solutions. Peritoneal macrophages and intestine, parietal peritoneum and omentum samples were obtained from the animals after 24 h. The alkaline single-cell microgel electrophoresis assay (comet assay) was performed on cells isolated from the solid tissues. Tail moment was applied as a basis of evaluation following image analysis. Our results indicate high levels of DNA strand breaks in the cells prepared from the omentum and intestine. We could also demonstrate a significant potentiating effect of the adsorbed carcinogen on the induction of DNA damage in the omentum. The parietal peritoneum and macrophages were not involved in the early genotoxic alterations under study. Our results support the molecular model of asbestos cocarcinogenesis, including both asbestos-induced deletions and mutations caused by a mutagen carried by the same fibres.

In plain English

This was an animal experiment. Female F-344 rats were given a single dose by stomach tube of 50 mg/kg of UICC crocidolite or anthophyllite asbestos fibres. The fibres were either untreated or had first adsorbed benzo[a]pyrene (BaP) from a water solution. Untreated control rats were also studied, with three rats per group. After 24 hours, DNA strand breaks were measured with the comet assay in macrophages from the peritoneal cavity and in cells from the parietal peritoneum, intestine and omentum. No DNA damage was seen in macrophages in any group. In the parietal peritoneum, a weak but statistically significant change appeared only in the crocidolite-plus-BaP group. Intestinal cells showed significant damage in every treated group. In the omentum, the treated groups differed significantly from controls, more so with BaP-coated fibres, and crocidolite-plus-BaP differed significantly from crocidolite alone. The study measured early DNA damage, not tumours. The authors concluded that these local effects could explain gastrointestinal and peritoneal tumours (for example mesothelioma) arising in the intestine and omentum. They added that their hypothesis still requires confirmation from studies of human populations.

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 comet assay for DNA strand breaks in rats after oral dosing)
• Who was studied: Female F-344 rats in five groups of three: untreated control (K), crocidolite (C), anthophyllite (A), crocidolite plus BaP (C/BaP) and anthophyllite plus BaP (A/BaP)
• Exposure: A single gavage dose of 50 mg/kg UICC crocidolite or anthophyllite fibres, either untreated or after adsorbing benzo[a]pyrene from an aqueous solution printed as 2.5 mg/ml. Animals were killed 24 hours after exposure.
• Main results:
  • No genotoxicity was observed in cells from the peritoneal cavity (macrophages) in any group.
  • In parietal peritoneum cells, a weak but statistically significant alteration was found only in the crocidolite plus BaP group.
  • Intestinal cells showed a significant genotoxic effect in each treated group.
  • In omentum samples, average tail moments differed significantly from the untreated control. The difference was more pronounced with BaP-adsorbed fibres.
  • In the omentum, the crocidolite plus BaP group also differed significantly from the crocidolite-only group.
• The authors' conclusion: The authors concluded that the local genotoxic effect of ingested amphibole fibres could explain gastrointestinal and peritoneal tumours (e.g. mesothelioma) arising in the intestine and omentum. They said the findings indirectly support their hypothesis that water-borne organic chemicals carried by the fibres play a role in tumour rates in populations drinking asbestos-contaminated water.
• Limitations the authors state:
  • The authors stated that their hypothesis still requires epidemiological confirmation.
  • The authors noted that the negative results in peritoneal cells and macrophages may be because these cells were not actually exposed in the first 24 hours.

Topics

Medical terms in this study, explained in our Lexicon: Amphibole Asbestos, Comet Assay, Asbestos Exposure, UICC, Crocidolite, Anthophyllite, Macrophage, Peritoneum.

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)
• Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene — S.O. Mikalsen, E. Rivedal, et al. (1988)
• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2006)
• In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos — C. Varga, G. Horváth, et al. (1996)
• Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene — J. Friemann, M. Varnai, et al. (1996)

Browse more research in Cancer Letters, or return to medical research.