A human cell system for detecting asbestos cytogenotoxicity in vitro

Our plain-English summary of A human cell system for detecting asbestos cytogenotoxicity in vitro, by T. Takeuchi, M. Nakajima, K. Morimoto (Mutation Research, 1999).

The study

• Authors: T. Takeuchi, M. Nakajima, K. Morimoto
• Journal: Mutation Research
• Published: 1999;438(1):63-70
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Crocidolite, a carcinogenic asbestos in humans, specifically induces mesothelioma. We investigated the cytogenotoxic effects of crocidolite in a human mesothelioma cell line, MSTO211H, and a human promyelocytic leukemia cell line, HL60. Using confocal laser scanning microscopy, we found that the MSTO211H cells had phagocytotic activity, whereas the HL60 cells did not. In the MSTO211H cells, crocidolite decreased the cell population and increased the numbers of polynucleated cells (PN) and tetraploid cells, and increased the coefficients of variation (CV) of DNA contents in G0/G1 cells and the formation of 8-hydroxydeoxyguanosine. In contrast, crocidolite showed none of these cytogenotoxic effects in HL60 cells. To investigate the importance of phagocytosis in the cytogenotoxicity of crocidolite, we sorted the crocidolite-phagocytosed cells from less-phagocytosed cells by fluorescence-activated cell sorting, and studied the differences in cytogenotoxicity between these two cell groups. We found significant increases in the numbers of PN and tetraploid cells and the CV in the crocidolite-phagocytosed cells compared to the less-phagocytosed cells. These findings indicate that MSTO211H cells are susceptible to the cytogenotoxic effects of asbestos due to their phagocytotic activity, and that the MSTO211H cell line is suitable for the detection of such effects on human cells by asbestos and other materials which need to be phagocytosed to exert their toxicity.

Copyright 1999 Elsevier Science B.V.

In plain English

This laboratory study tested crocidolite asbestos on two kinds of human cells grown in dishes: a commercially available mesothelioma cell line called MSTO211H and a promyelocytic leukemia cell line called HL60. No people or workers were studied. Under the microscope, the mesothelioma cells took up (engulfed) crocidolite fibers and latex beads, while the HL60 cells did not. In the mesothelioma cells only, crocidolite lowered the number of cells as the dose rose, to 49.9% of untreated cells at 30 micrograms per millilitre. It also increased the number of cells with more than one nucleus, cells with double the normal DNA content, and the variation in DNA content. It slightly increased a marker of oxidative DNA damage (8-hydroxydeoxyguanosine). When treated mesothelioma cells were sorted, those that had taken up more fiber showed significantly greater changes than those that had taken up less. The authors noted that the extra nuclei might reflect blocked cell division rather than genetic damage. The authors concluded that this cell system is useful for evaluating these effects of asbestos and other materials that must be taken up by cells to act.

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 human cell lines
• Who was studied: Two human cell lines grown in culture: the mesothelioma cell line MSTO211H (from the American Type Culture Collection) and the promyelocytic leukemia cell line HL60 (from the Japanese Cancer Research Resource Bank). No human subjects.
• Exposure: Crocidolite asbestos supplied by the National Centre for Occupational Health, Johannesburg, South Africa. It was added to the cells for 24 hours at 0, 3, 10 and 30 micrograms per millilitre (printed as 'mgrml' in the scan).
• Main results:
  • MSTO211H mesothelioma cells took up (phagocytosed) fluorescent latex beads and crocidolite; HL60 cells did not.
  • Crocidolite decreased the cell population and induced cells with more than one nucleus (polynucleated cells) only in MSTO211H cells. In MSTO211H, cell numbers fell to 49.9% of control at 30 micrograms per millilitre; in HL60 the figure was 94.8%. The increase in polynucleated cells depended on the crocidolite concentration.
  • Crocidolite increased the number of tetraploid cells (double DNA content) only in MSTO211H cells.
  • In MSTO211H cells, crocidolite increased the coefficient of variation of DNA content in G0/G1 cells, from 4.46% without crocidolite to 5.00% with 30 micrograms per millilitre (n = 9, p less than 0.001).
  • In MSTO211H cells, crocidolite slightly increased the oxidative DNA damage marker 8-hydroxydeoxyguanosine, from 0.55 to 0.74 per 10^5 dG with 30 micrograms per millilitre (n = 3, p less than 0.05). The authors judged this increase was not the cause of the other effects.
  • Among crocidolite-treated MSTO211H cells sorted by fiber uptake, the cells that had taken up more crocidolite had significantly higher levels of polynucleated cells, G2/M (tetraploid) cells and DNA-content variation than the cells that had taken up less (p less than 0.001). Unsorted cells showed intermediate values.
• The authors' conclusion: The authors concluded that MSTO211H cells are susceptible to the cell- and DNA-damaging effects of asbestos because they take up fibers. They concluded the system is useful for evaluating asbestos and other materials that must be phagocytosed to exert their toxicity. They also suspected that physical interactions between engulfed crocidolite and cell components might be the most important cause of asbestos carcinogenesis.
• Limitations the authors state:
  • The increase in polynucleated cells might not reflect genetic damage; crocidolite may only have blocked cell division.
  • Chemical inhibitors of phagocytosis could not be used because they were toxic to MSTO211H cells (cytochalasin B itself blocked cell division), so cells were sorted by fiber uptake instead.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Carcinogenic, Mesothelioma, Phagocytosis.

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