An in vitro lung epithelial cell system for evaluating the potential toxicity of inhalable materials

Our plain-English summary of An in vitro lung epithelial cell system for evaluating the potential toxicity of inhalable materials, by A.P. Li (Food and Chemical Toxicology, 1986).

The study

• Author: A.P. Li
• Journal: Food and Chemical Toxicology
• Published: 1986;24(6-7):527-34
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Assays have been developed using a lung epithelial cell strain, LEC, for evaluating the cytotoxicity and genotoxicity of gases, vapours, particles and fibres. LEC was derived from an adult male Fischer 344 rat and was cultured continuously in vitro for over 60 passages. The cells had an epithelial morphology, a near-diploid modal chromosome number of 43-44, and properties of untransformed cells. Lamellar inclusion bodies were found in the cytoplasm, suggesting that LEC originated from the type II alveolar cells. The ability to LEC to metabolize xenobiotics was demonstrated by the formation of polar metabolites from benzo[a]pyrene, the induction of gene mutation by promutagens in a metabolically incompetent cell line (Chinese hamster ovary cells) after co-cultivation with LEC, and the induction of sister chromatid exchange in LEC by promutagens. LEC will grow on collagen gel in the absence of an overlying medium, thereby constituting an in vitro exposure system closely resembling lung epithelium in vivo. The cytotoxic potential of inhalable agents, including nitrogen dioxide, phenol vapours, formaldehyde, automobile exhaust, titanium dioxide and chrysotile and crocidolite forms of asbestos was studied. The in vitro cytotoxicity appeared to correlate well with the known in vivo pulmonary toxicity of the substances studied. Using chromosomal-aberration induction as an endpoint, chrysotile asbestos was found to be genotoxic to LEC. Our results suggest that LEC may be a useful in vitro system for the evaluation of the toxic potential of inhalable materials.

In plain English

This laboratory paper described LEC, a lung epithelial cell strain taken in 1980 from a male Fischer 344 rat and grown for over 60 passages. It also reviewed using the strain to test inhaled substances. The cells contained lamellar inclusions typical of type II alveolar cells, made surfactant lipid and could convert some chemicals into mutagenic forms. Five mineral dusts were tested for cell damage: UICC crocidolite, intermediate chrysotile, no. 5 chrysotile, calcium sulphate fibres and titanium dioxide. Crocidolite and chrysotile were highly toxic, while titanium dioxide and calcium sulphate fibres showed relatively low toxicity. With chrysotile, the share of cells with chromosome damage rose with dose: 0% of 100 untreated cells, then 3% of 100, 7% of 100, 14.5% of 76 and 21.6% of 88 cells at 0.2, 0.4, 1.0 and 2.0 micrograms per square centimetre. Fewer cells were scored at the higher doses because of toxicity. The author concluded the system may be useful for evaluating inhalable materials. The author noted drawbacks: loss of differentiation in culture, only one cell type and an abnormal chromosome number.

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) laboratory study that also reviews the author's earlier work characterizing and using the same rat lung cell strain
• Who was studied: LEC, a lung epithelial cell strain derived from one 20-week-old male specific-pathogen-free Fischer 344 rat, isolated in November 1980 and cultured for over 60 passages (Monsanto Company laboratory, St Louis, USA)
• Exposure: Five mineral dusts tested for cytotoxicity: UICC crocidolite, intermediate chrysotile, no. 5 chrysotile, calcium sulphate fibres and titanium dioxide. Chrysotile was tested for chromosome damage at 0.2, 0.4, 1.0 and 2.0 micrograms per square centimetre. Other agents discussed include nitrogen dioxide, phenol, formaldehyde, coal-gasifier volatiles, diesel exhaust and chemical mutagens.
• Main results:
  • LEC cells could synthesize surfactant lipids and contained lamellar inclusions characteristic of type II alveolar cells
  • The chemical DMBA was mutagenic to Chinese hamster ovary cells only when LEC cells were present, indicating that LEC converted it to mutagenic metabolites
  • In the LDH release assay, both crocidolite and chrysotile asbestos were highly cytotoxic to LEC cells
  • Titanium dioxide and the calcium sulphate fibre showed relatively low cytotoxicity to LEC cells
  • Aberrant LEC cells after chrysotile treatment: 0% of 100 medium-only cells; 3% of 100 at 0.2; 7% of 100 at 0.4; 14.5% of 76 at 1.0; 21.6% of 88 at 2.0 micrograms per square centimetre
  • Chrysotile produced a dose-related induction of both chromosomal aberrations and near-tetraploid cells
  • The authors stated that the in vitro cytotoxicity of the mineral dusts appeared to correlate well with their expected in vivo toxicity
• The authors' conclusion: The author concluded that LEC may be a useful in vitro system for evaluating the toxic potential of inhalable materials
• Limitations the authors state:
  • The cells undergo de-differentiation in culture
  • The system represents only one lung cell type (type II)
  • The cells have an aneuploid karyotype and may have altered properties
  • Fewer than 100 cells could be scored at the two highest chrysotile doses because of high cytotoxicity

Topics

Medical terms in this study, explained in our Lexicon: Genotoxicity, Collagen, Epithelium, Chrysotile, Crocidolite.

Related studies

• In vitro activity of silicon carbide whiskers in comparison to other industrial fibers using four cell culture systems — N.F. Johnson, M.D. Hoover, et al. (1992)
• Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells — T.A. Stueckle, D.C. Davidson, et al. (2017)
• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Evaluating chemical risks: results of a survey of the British Toxicology Society — P. Slovic, T. Malmfors, et al. (1997)
• Asbestos causes translocation of p65 protein and increases NF-kappa B DNA binding activity in rat lung epithelial and pleural mesothelial cells — Y.M. Janssen, K.E. Driscoll, et al. (1997)
• Pulmonary toxicity of wollastonite in vivo and in vitro — E. Tátrai, Z. Kováciková, et al. (2004)

Browse more research in Food and Chemical Toxicology, or return to medical research.