Inhibition of asbestos-induced transformation of rat pleural mesothelial cells in co-culture with rat macrophages

Our plain-English summary of Inhibition of asbestos-induced transformation of rat pleural mesothelial cells in co-culture with rat macrophages, by I.V. Kravchenko, V.A. Furalyov, L.A. Vasylieva, et al (Teratogenesis, Carcinogenesis, and Mutagenesis, 2001).

The study

• Authors: I.V. Kravchenko, V.A. Furalyov, L.A. Vasylieva, L.N. Pylev
• Journal: Teratogenesis, Carcinogenesis, and Mutagenesis
• Published: 2001;21(5):315-23
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this work was to investigate the influence of macrophages on the process of rat pleural mesothelium cells (RPMC) transformation in vitro. For this purpose prolonged many-passage co-cultivation of rat pleural mesothelial cells and rat peritoneal macrophages was performed both in the presence (to study macrophage influence on asbestos-induced morphologic transformation) and in the absence (to study spontaneous transformation) of asbestos. It was shown that spontaneous transformation of RPMC slightly accelerated in the co-cultures, whereas asbestos-induced transformation was strongly inhibited. For instance, RPMC acquired the ability to form multilayer cell growth foci and colonies in semisolid agar at 22-24 passages in the absence and at 14-16 passages in the presence of asbestos, while in co-culture with macrophages these signs of transformation appeared at 17-19 passages without asbestos treatment and were not observed at the 40th passage under exposure to asbestos. It was shown that the observed inhibition of transformation was caused by preferential depletion of transformed cells in co-cultures of mesothelium and macrophages in the presence of asbestos: when equal concentrations of macrophages and asbestos were taken, the viability of early-passage RPMC was greater as compared with late passages, and the viability of late-passage RPMC was greater than that of mesothelioma cells. The amount of late-passage RPMC and mesothelioma cells able to form colonies in semisolid media was also drastically decreased in these conditions. These findings suggest that though macrophages can influence the process of asbestos-induced mesothelium transformation by different ways, as a whole the inhibitory action appears to be the strongest.

Copyright 2001 Wiley-Liss, Inc.

In plain English

This was a laboratory study of cells grown in dishes. Cells from the lining of the chest cavity (pleural mesothelial cells) of Wistar rats were grown alone or together with rat macrophages, a type of immune cell, through many rounds of subculturing, called passages. Some cultures were repeatedly treated with chrysotile asbestos. The authors recorded when the cells first showed signs of transformation: growing in multiple layers and forming colonies in soft agar. Without asbestos, these signs appeared at passages 22–24 in mesothelial cells grown alone and at passages 17–19 when macrophages were present. With asbestos, they appeared at passages 14–16 in mesothelial cells alone. In cultures given both asbestos and macrophages, no such signs had appeared by passage 40. In further tests, the combination of macrophages and asbestos was more toxic to later-passage cells and to rat mesothelioma cells than to early-passage cells, and it reduced their colony growth in soft agar. The authors concluded that the inhibition came from the toxic action of macrophages and asbestos on malignant cells. They noted that it remained to be seen whether these laboratory results would be confirmed in living animals.

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: long-term co-culture of rat pleural mesothelial cells with rat peritoneal macrophages, with and without asbestos, plus cytotoxicity and soft-agar colony assays
• Who was studied: Four lines of rat pleural mesothelial cells (RPMC) from Wistar rats, co-cultured with peritoneal macrophages from rats. Three rat mesothelioma cell lines, taken from tumors in Wistar rats given intraperitoneal injections of chrysotile asbestos, were used in the cytotoxicity tests. The work came from a cancer research center in Moscow, Russia. Dates are not given.
• Exposure: Chrysotile asbestos from the Bazhenov deposit (50% of fibers less than 1 µm thick, 70% of fibers 10–50 µm long), at 5 µg/cm2. It was first applied at passage 4 for 3 days and then at each passage. Cultures were with or without 4 × 10^5 macrophages per flask. In the cytotoxicity tests, macrophage numbers varied.
• Main results:
  • Mesothelial cells grown alone showed signs of transformation (multilayer growth foci and growth in semisolid medium) at passages 22–24 without asbestos and at passages 14–16 with asbestos.
  • In mesothelial cells co-cultured with macrophages without asbestos, transformation signs appeared slightly earlier, at passages 17–19.
  • In mesothelial cells co-cultured with macrophages and asbestos, no multilayer growth foci or soft-agar colonies were seen up to passage 40.
  • Asbestos alone killed less than 5% of mesothelial cells. In co-culture with macrophages, asbestos raised mesothelial cell mortality to 10–30%.
  • With equal amounts of macrophages and asbestos, early-passage mesothelial cells survived better than late-passage cells, and late-passage cells survived better than mesothelioma cells.
  • Many passage-8 mesothelial cells survived even the highest macrophage number used (1.3 × 10^6) together with asbestos.
  • With asbestos, about 5.5 × 10^4 macrophages on average caused pronounced toxicity to passage-30 mesothelial cells, while 2.2 × 10^3 macrophages produced a significant toxic effect on mesothelioma cells.
  • Asbestos alone had only a weak toxic effect on the cells.
  • With asbestos, 2.8 × 10^5 macrophages completely prevented mesothelioma cells from growing in soft agar. Without asbestos, even 1.3 × 10^6 macrophages did not fully stop colony formation (data not shown in the article).
• The authors' conclusion: The authors concluded that the inhibition of asbestos-induced transformation was due to the toxic action of macrophages and asbestos on malignant mesothelial cells, both cells transformed in culture and cells from mesotheliomas that developed in rats.
• Limitations the authors state:
  • The authors noted that it is an open question whether their laboratory (in vitro) results would be confirmed in living animals (in vivo).

Mines named here

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

• Bajenova district, Bajenova district, about 90 km northeast of Sverdlovsk, Russia

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Macrophage, Mesothelium, Mesothelioma.

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• In vitro transformation of rat pleural mesothelial cells by chrysotile fibres and/or benzo[a]pyrene — M.J. Paterour, J. Bignon, et al. (1985)
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• Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells — I.V. Kravchenko, V.A. Furalyov, et al. (2003)

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