A new in vitro cellular system for the analysis of mineral fiber biopersistence

Our plain-English summary of A new in vitro cellular system for the analysis of mineral fiber biopersistence, by H. Dika Nguea, A. de Reydellet, P. Lehuédé, et al (Archives of Toxicology, 2008).

The study

• Authors: H. Dika Nguea, A. de Reydellet, P. Lehuédé, A. de Méringo, A. Robé, A. Le Faou, B.H. Rihn
• Journal: Archives of Toxicology
• Published: 2008;82(7):435-43
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The toxicity of mineral fibers, whether they are natural or man made (MMMF), is usually evaluated in vivo using biopersistence tests in rodents. Development of an in vitro cellular model would be worthwhile in order to reduce, refine and finally replace animal models. For this purpose, we developed an in vitro assay using human monocytic cell line (U-937) to evaluate a new manufactured rock wool fiber (HDN) biodegradation. Experiments on earlier known mineral fibers asbestos (crocidolite) and glass wool fibers (CM44) were also performed. U-937 responded to HDN and CM44 only if they were activated. Among the different activators we used, Escherichia coli living cells as well as FS were the most efficient as evidenced by alterations of HDN and CM44 surface, detected by scanning electron microscopy, and by the measure of silicon released from the rock wool fibers. Asbestos fibers were not degraded when incubated in the presence of living bacteria. The MMMF modifications were function of the fiber composition, the time of exposure to activated cells and the concentration of activators. The pattern of MMMF degradation by our in vitro system was in accordance with those observed in an in vivo study, thus indicating that the fiber degradation by macrophage cells activated by E. coli living cells as well as FS is a valuable system to assess mineral fibers' biopersistence.

In plain English

This laboratory study tested whether a human immune cell line (U-937, which can develop into macrophages) could replace animal tests of how long mineral fibers persist in the lung. The authors exposed the cells to a new rock wool fiber (HDN), a glass wool fiber (CM44) and crocidolite asbestos. On their own, the cells engulfed or covered fibers but did not degrade them. When the cells were kept with living E. coli bacteria for 7 days, HDN fibers developed surface pits (erosion) and CM44 fibers showed surface dissolution, but crocidolite was unchanged. Filtered liquid from an E. coli culture, or the signaling proteins IL6 or TNF-alpha, also led to erosion of HDN. With filtered E. coli liquid, silicon released from HDN after 14 days was about 10 times the amount after 2 days. In rats given HDN into the windpipe, fibers recovered after 1 month showed the same pattern of pits and holes, but more pronounced. The authors concluded the system could be a valuable tool for assessing biopersistence, but said further work is needed before it becomes a standardized test.

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 cell-culture (in vitro) experiment, compared with an in vivo rat intratracheal instillation experiment
• Who was studied: human monocytic cell line U-937; rats given HDN fibers by intratracheal instillation (number of rats not stated)
• Exposure: new manufactured rock wool fiber (HDN) and glass wool fiber (CM44), both supplied by Saint Gobain Insulation, plus crocidolite asbestos
• Main results:
  • U-937 cells without an activating agent engulfed or covered the fibers, but the fibers were not degraded
  • In the presence of living E. coli bacteria for 7 days, HDN rock wool fibers showed surface erosion: numerous pits about 100 nm wide and up to 13% of fiber diameter deep
  • Under the same conditions, CM44 glass wool fibers showed surface dissolution rather than pitting
  • Under the same conditions with living E. coli, the surface of crocidolite fibers was unchanged
  • HDN fibers were altered when the cells were given IL6 or TNF-alpha, but remained unchanged with LPS (a bacterial cell-wall component)
  • Degradation occurred with E. coli but not with the bacteria B. subtilis or S. aureus
  • In rats, HDN fibers recovered by lung lavage after 1 month showed erosion more pronounced than in the 7-day cell system, with the same pattern of pits and holes
  • With cells plus filtered E. coli culture liquid, silicon released from HDN fibers after 14 days was about 10 times that measured after 2 days
  • Silicon release was about 50-fold higher at the highest than at the lowest concentration of filtered E. coli culture liquid
  • CM44 glass wool was degraded more than HDN rock wool. The authors compared this ranking with lung half-lives taken from earlier in vivo studies they cite: more than 120 days for crocidolite, 25 days for HDN and 12.8 days for CM44
• The authors' conclusion: The authors concluded that the U-937 system activated by living E. coli, E. coli culture medium, IL6 or TNF-alpha could be a valuable tool to assess biopersistence, but that further analysis is needed for a standardized test
• Limitations the authors state:
  • The system needs to be evaluated on a wider range of fibers with different compositions
  • The agent that activates the cells and the molecular mechanism of degradation have not been identified

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, biopersistence, Crocidolite, Scanning Electron Microscopy (SEM), Macrophage.

Related studies

• Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers — G. Cardinali, D. Kovacs, et al. (2006)
• The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats — T.W. Hesterberg, G.A. Hart, et al. (1998)
• An experimental approach to the evaluation of the biopersistence of respirable synthetic fibers and minerals — D.M. Bernstein, R. Mast, et al. (1994)
• Evaluation of cellular toxicity of TAFMAG, a natural substitute for asbestos from China — H.J. Kim, H.Y. Nam, et al. (2005)
• Models for mesothelioma incidence following exposure to fibers in terms of timing and duration of exposure and the biopersistence of the fibers — G. Berry (1999)
• An in vitro/in vivo study into the short term effects of exposure to mineral fibres — A. Clouter, C.E. Houghton, et al. (1996)

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