Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma

Our plain-English summary of Cellular effects of asbestos and other fibers: correlations with in vivo induction of pleural sarcoma, by L.E. Lipkin (Environmental Health Perspectives, 1980).

The study

• Author: L.E. Lipkin
• Journal: Environmental Health Perspectives
• Published: 1980;34:91-102
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The phenomenon of fiber-induced cytotoxicity to P388D1 macrophagelike cells has been demonstrated to parallel (thus far without exception) the probability that the fiber will induce a pleural sarcoma (mesothelioma) in rats. This startling parallel in both cases seems to be essentially independent of the chemical nature of the fiber and correlates best with the presence of fibers greater than 8 micrometers in length and fibers with diameters in the range 0.5 to 1.0 micrometer (Stanton Hypothesis). In both systems evidence has been produced which cast strong doubts on any role played by absorbed (or adherent) impurities. The existence of multiple physical forms of the same chemical moiety (aluminum oxide, dihydroxy-sodium aluminum carbonate, borosilicate glass, etc.,) provides additional test material for the chemical independence corollary. The similar, cytotoxic or sarcomatogenous behavior of chemically different materials (e.g. amosite, chrysotile, aluminum oxide) exhibits the necessary converse argument. As long as the fiber size-shape dependency effect was limited to whole animal phenomena, such as tumor induction, one could make implicitly what were essentially statistical or probabilistic inferences involving transport and/or distribution of fibers to account for the physical effect. The demonstration of strict parallelism at the cellular level in vitro suggests the possibility that in the case of durable fiber toxicology we are dealing with a form of cell-solid interaction in which physical properties for which we have as yet no known receptors play a prominent role.

In plain English

This laboratory study asked whether fibers that harm cells in a dish match the fibers that earlier rat experiments by Stanton and Layard found likely to cause pleural sarcoma (mesothelioma). The author exposed a mouse macrophage-like cell line, P388D1, to fibers at 10, 50 or 100 micrograms per cubic centimeter and counted cells over 72 hours. The fibers were UICC amosite and chrysotile asbestos and non-asbestos fibers from Stanton and Layard's lots: several forms of aluminum oxide and of dawsonite, potassium octatitanate, silicon carbide and borosilicate glass. Amosite and chrysotile reduced cell numbers, more so at higher concentrations. Within aluminum oxide, and within dawsonite, chemically identical forms differed widely in effect. Their cytotoxicity order, measured by changes in cell number, matched the order of Stanton and Layard's published tumor probabilities. For example, aluminum oxide HC, the most toxic to cells, had a published probability of 0.70, while form No. 5 had 0.05. Crocidolite was also toxic to the cells. Talc and celite, which the article calls nonfibrous, repeatedly were not. Cytotoxicity was compared by ranking, not by numerical values. The author concluded that fiber size and shape, rather than chemistry, may drive both effects.

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: In vitro (cell culture) cytotoxicity experiments, with results set beside previously published rat pleural sarcoma probabilities from Stanton and Layard
• Who was studied: P388D1 macrophage-like cells, an established cell line originally derived from a tumor in a DBA/2 mouse, grown in flasks
• Exposure: UICC amosite, chrysotile and crocidolite asbestos, plus non-asbestos fibers from the same lots used by Stanton and Layard (aluminum oxide forms, dawsonite forms, potassium octatitanate, silicon carbide, borosilicate glass MOL). Concentrations were 10, 50 or 100 micrograms per cubic centimeter, observed over 72 hours.
• Main results:
  • UICC amosite reduced P388D1 cell numbers, especially at higher concentrations
  • At the higher concentrations (50 and 100 micrograms per cubic centimeter), UICC chrysotile left fewer cells at 72 hours than at the start, indicating some cell death
  • For four aluminum oxide forms, the order of cytotoxicity was HC, then No. 3, then No. 2, then No. 5. This was the same order as Stanton and Layard's probability of pleural sarcoma. Cytotoxicity was judged only by change in cell number.
  • In Table 1, aluminum oxide No. 5 showed no cytotoxicity (0) and had a Stanton and Layard sarcoma probability of 0.05. Aluminum oxide HC was rated +++ with a probability of 0.70.
  • Dawsonite samples V and VII were about as cytotoxic as amosite and were highly likely in Stanton's rat work to produce pleural sarcomas. Sample VI was considerably less cytotoxic and much less likely to produce them.
  • Potassium octatitanate and silicon carbide were rated +++ for cytotoxicity, each with a published sarcoma probability of 1.00. Borosilicate glass MOL was rated +++ with a probability of 0.85.
  • For potassium octatitanate, the dose response appeared to increase steadily with dose but was not proportional to it
  • Crocidolite and chrysotile from Rockville quarry rock were cytotoxic. Talc and celite, described as nonfibrous, repeatedly showed no cytotoxic effect.
• The authors' conclusion: The author concluded that the close parallel between cell toxicity and rat pleural sarcoma suggests the length and diameter limits proposed by Stanton may apply to cytotoxicity too. The author suggested durable fibers may act through a cell-solid interaction driven by physical properties.
• Limitations the authors state:
  • Cytotoxicity was compared by rank ordering rather than expressed as numerical values. Better statistical measures were still being developed.
  • Differences in starting cell numbers complicated comparisons, and adjusting for them was only partially successful
  • A simple mass measure of dose is unsuitable, because fibers outside the effective size range dilute the few effective fibers
  • Critical experiments with fiber samples of precisely known length and diameter had not yet been done
  • The cell system is only a partial model, and long-term effects of repeated fiber uptake were not evaluated
  • The Stanton Hypothesis is limited to pleural tumors and is not claimed for lung or bronchial tumors

Topics

Medical terms in this study, explained in our Lexicon: Sarcoma, Mesothelioma, Stanton Hypothesis, Amosite, Chrysotile.

Related studies

• Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases — M. Miettinen, Z. Wang, et al. (2015)
• Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans — K.R. Maples, N.F. Johnson (1992)
• Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings — M. Yegles, X. Janson, et al. (1995)
• Internalization of Libby amphibole asbestos and induction of oxidative stress in murine macrophages — D.J. Blake, C.M. Bolin, et al. (2007)
• In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays — B.T. Mossman (1990)
• Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite — D.L. Coffin, L.D. Palekar, et al. (1983)

Browse more research in Environmental Health Perspectives, or return to medical research.