Morphological transformation in vitro of normal human fibroblasts by chrysotile

Our plain-English summary of Morphological transformation in vitro of normal human fibroblasts by chrysotile, by L.B. Joseph, R.E. Stephens, A.C. Ottolenghi, et al (Environmental Health Perspectives, 1983).

The study

• Authors: L.B. Joseph, R.E. Stephens, A.C. Ottolenghi, P.D. Lipetz, H.A. Newman
• Journal: Environmental Health Perspectives
• Published: 1983;51:17-22
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies. Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due--at least in part--to a lack of control over cytokinesis.

In plain English

This laboratory study exposed normal human skin (dermal) fibroblasts grown in culture to a single dose of NIEHS short chrysotile or NIEHS amosite. Control cells received salt solution only. The authors then watched the cells under the microscope while growing and splitting them repeatedly over about two months. Within 12 hours, chrysotile-treated cells became elongated and some appeared to have cleared nuclei. Amosite did not cause the same changes. Two days after the first split, cells with two nuclei appeared in the chrysotile-treated cultures. The authors also reported giant cells with 2 to 11 nuclei. At passage 23, chrysotile-treated cells reached a density at confluence of 5.3 x 10^3 cells per square centimeter. Control cells reached 5.5 x 10^4 and amosite-treated cells 4.2 x 10^4. By about two months, chrysotile-treated cells had lost typical fibroblast shape. Electron microscopy found chrysotile in the cytoplasm but not in the nucleus. It found no detectable differences between control and amosite-treated cells. The authors called their indications preliminary. They suggested the changes are due at least in part to a lack of control over cytokinesis, the step in which a dividing cell splits in two.

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. A single exposure to asbestos was followed by repeated passaging and observation by light and transmission electron microscopy.
• Who was studied: Normal human dermal fibroblasts (a cell line called CI), used at passage 16 and 80% confluence, studied at The Ohio State University, Columbus, Ohio. Control cells received phosphate buffered saline only.
• Exposure: A single application of NIEHS short chrysotile or NIEHS amosite in phosphate buffered saline. The concentration is printed as 63 per square centimeter, with the unit damaged in the scan.
• Main results:
  • At 12 hours, chrysotile caused definite elongation of the fibroblasts and apparently cleared nuclei. Amosite did not cause the same changes.
  • At 48 hours after chrysotile exposure, the fibroblasts became very elongated and pulled apart from each other.
  • Two days after the first passage, binucleated cells began to appear in the chrysotile-treated cultures.
  • Multinucleated giant cells with 2 to 11 nuclei per cell became more numerous over time in culture.
  • One passage after treatment (passage 17), cell density at confluence was 1.41 x 10^5 cells per square centimeter in controls, 1.26 x 10^5 in amosite-treated cells and 3.2 x 10^4 in chrysotile-treated cells.
  • At passage 23, cell density at confluence was 5.3 x 10^3 cells per square centimeter in chrysotile-treated cells, 5.5 x 10^4 in controls and 4.2 x 10^4 in amosite-treated cells.
  • About two months after exposure, chrysotile-treated cells lacked typical fibroblast shape and showed vacuolation and granulation of the cytoplasm.
  • At about two months, amosite-treated cells showed increased granularity of the cytoplasm but no change in growth pattern.
  • Electron microscopy found no detectable differences between control and amosite-treated cells.
  • In chrysotile-treated cells, electron microscopy found chrysotile in the cytoplasm but none in the nucleus. It also found stacked endoplasmic reticulum, an immature nucleus with cleared chromatin, and more lysosomes.
• The authors' conclusion: The authors stated that chronic effects of asbestos can be induced by a one-time exposure. They called their indications preliminary and suggested that the changes are due, at least in part, to a lack of control over cytokinesis.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibroblast, Chrysotile, Granuloma, Mesothelioma.

Related studies

• Chrysotile asbestos induces PDGF-A chain-dependent proliferation in human and rat lung fibroblasts in vitro — J.A. Lasky, J.C. Bonner, et al. (1996)
• Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts — M.J. Chang, N.P. Singh, et al. (1983)
• Sister-chromatid exchange and cell kinetics in CHO-K1 cells, human fibroblasts and lymphoblastoid cells exposed in vitro to asbestos and glass fibre — G. Casey (1983)
• Xeroderma pigmentosum fibroblasts are more sensitive to asbestos fibers than are normal human fibroblasts — L.L. Yang, R.E. Kouri, et al. (1984)
• Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts — R.W. Hart, F.B. Daniel, et al. (1980)
• Kerosene soot genotoxicity: enhanced effect upon co-exposure with chrysotile asbestos in Syrian hamster embryo fibroblasts — M. Lohani, E. Dopp, et al. (2000)

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