Investigations of DNA Damage Produced by Asbestos Fibers in Rat Pleural Mesothelial Cells

Our plain-English summary of Investigations of DNA Damage Produced by Asbestos Fibers in Rat Pleural Mesothelial Cells, by M.C. Jaurand (Inhalation Toxicology, 2000).

The study

• Author: M.C. Jaurand
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:183-7
• Read it: PubMed · Publisher

Abstract

Asbestos fibers have long been considered nongenotoxic because of the absence of point asbestos-treated cells mutations in several assays. More recently, some studies have demonstrated that various kinds of DNA damage were observed in asbestos-treated cells, namely, base hydroxylation, DNA adducts, and DNA breaks. The occurrence of DNA breakage has been mostly suggested by indirect methods. We investigated DNA damage produced by Rhodesian chrysotile fibers in a model of normal rat pleural mesothelial cells (RPMC) developed in our laboratory, by different approaches. DNA breakage and repair of DNA damage were evidenced by the enhancement of the activity of poly(ADP)ribose polymerase (PARP) and of unscheduled DNA synthesis, and were suggested by cell cycle arrest in asbestos-exposed RPMC. In growing cells, a cell cycle arrest was observed at the G1-S transition. DNA breakage was also demonstrated by the formation of comets in single-cell gel electrophoresis (SCGE) assay. The results showed that comets were generated by asbestos, as assessed by the significant increase in mean tail length and mean tail moment after exposure to asbestos. In RPMC-TSV40 (i.e., RPMC in which the protein was p53 inactivated by infection with a retroviral recombinant encoding the large T antigen of the SV40 virus), the comet parameters were moderately enhanced. Regarding previous results of an impairment of DNA repair in RPMC-TSV40, the SCGE results suggest that chrysotile caused DNA breakage in both RPMC and RPMC-TSV40. Moreover, these findings lead to the hypothesis that DNA repair was impaired in RPMC-TSV40.

In plain English

This was a short laboratory study by a single author, using rat pleural mesothelial cells grown in culture, not people or live animals. It tested whether chrysotile asbestos (UICC Rhodesian chrysotile) breaks DNA in these cells. Two kinds of cells were used: normal cells, and cells altered with a gene for the SV40 virus large T antigen, which inactivates the p53 protein. Cells were exposed to several doses for 24 hours. DNA damage was measured in 150 randomly selected cells with the comet assay, a test in which broken DNA forms a 'tail'. Without asbestos, about 85% of cells of both types showed no comet. Chrysotile increased tail length and mean tail moment, but less in the altered cells than in the normal cells. In normal cells, comets appeared at a low, nontoxic concentration of 0.5 micrograms per square centimeter. The author concluded that asbestos fibers produced DNA breakage in both cell types. The author also concluded that p53 inactivation was associated with less DNA breakage, possibly linked to impaired DNA repair. The study did not examine whether comet formation was related to toxicity.

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 experiment using the alkaline comet assay (single-cell gel electrophoresis)
• Who was studied: Cultured normal rat pleural mesothelial cells (RPMC) and RPMC transformed with the SV40 large T antigen gene (RPMC-TSV40, p53 inactivated); comets analyzed in 150 randomly selected cells; laboratory in Creteil, France; dates not stated
• Exposure: UICC Rhodesian chrysotile fibers at several doses for 24 hours (only 0.5 micrograms per square centimeter is named in the text)
• Main results:
  • In both untreated normal RPMC and untreated RPMC-TSV40, most cells (about 85%) showed no comet, indicating undamaged DNA
  • Exposure to chrysotile increased both tail length and mean tail moment (DNA breakage), compared with untreated controls
  • These comet parameters were less increased in the SV40-transformed cells (RPMC-TSV40) than in the normal RPMC
  • In normal RPMC, comets appeared at a low, nontoxic concentration of 0.5 micrograms per square centimeter
• The authors' conclusion: The author concluded that asbestos fibers produce DNA breakage in both normal and SV40-transformed mesothelial cells, and that p53 inactivation is associated with a reduction in the extent of DNA breakage, possibly related to impaired DNA repair
• Limitations the authors state:
  • The author states that whether comet formation is related to toxicity was not investigated

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, DNA adducts, Chrysotile, SV40.

Related studies

• Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro — H. Dong, A. Buard, et al. (1994)
• DNA damage in bronchial epithelial and mesothelial cells with and without associated crocidolite asbestos fibers — J. Nygren, S. Suhonen, et al. (2004)
• Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and apoptosis in mesothelial cells — W. Liu, J.D. Ernst, et al. (2000)
• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Effects of asbestos on initiation of DNA damage, induction of DNA-strand breaks, P53-expression and apoptosis in primary, SV40-transformed and malignant human mesothelial cells — B. Burmeister, T. Schwerdtle, et al. (2004)
• Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity — K. Hattori, K. Nakadate, et al. (2017)

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