Cultured cell lines are routinely used for in vitro toxicity screens, reducing the requirement for animal studies during the development of new pharmaceutical, agrochemical and cosmetic products. The foetal rat lung epithelial (FRLE) cell line was originally derived from alveolar type II cells (ATII) of the lung. The aims of this study were to further characterise FRLE cells and investigate their potential for screening for pneumotoxins. The cells were found to have retained some of the features of their progenitor cells, namely the expression of cytokeratin proteins, specifically cytokeratin 18, and the ability to actively accumulate the non-selective contact herbicide paraquat. However, the cells have lost the ability to synthesise surfactant protein mRNA and no longer contain multiple lamellar bodies. Toxins that damage ATII cells in vivo (cadmium chloride, cobalt chloride and paraquat) were found to induce cytotoxicity in FRLE cells, as did the non-specific pneumotoxin nitrofurantoin, and hydrogen peroxide. However, the cells were less sensitive to the effects of compounds that require metabolic activation (1-nitronaphthalene, coumarin and butylated hydroxytoluene) and the hepatotoxin bromobenzene. Thus, FRLE cells appear to be a good in vitro model for monitoring the potential toxicity to ATII cells and could be used as an initial screen for pneumotoxicity.

Genomics technology offers a way of detecting the effects of a toxin on the expression of many genes in a single experiment. We have previously partially characterised a foetal rat lung epithelial (FRLE) cell line and shown that it is suitable for use in a pneumocytotoxicity screen. In this study, we wanted to ascertain whether we could use alterations in FRLE cell gene expression as a sensitive marker of cell stress. Sodium butyrate and etoposide were shown to arrest FRLE cell cycle at G0/G1 and G2/M phase of the cell cycle, respectively and this was associated with a decrease in the number of cells in culture. Following 24h of culture both compounds caused a statistically significant increase in the mRNA levels of the cell cycle inhibitory protein, gadd153, whereas p21 was statistically altered by etoposide only. Hydrogen peroxide induced growth arrest at low concentrations (≤250μM) following 24h of culture. We could not detect an increase in apoptosis or in the mRNA levels of the pro-apoptotic protein bax in FRLE cells following culture with hydrogen peroxide or etoposide. Thus, it was possible to correlate cellular perturbations in FRLE cells with alterations in gene expression, demonstrating that these cells are suitable for use in a toxicity screen.

Conference Abstract| October 01 2000 Foetal Rat Lung Epithelial (FRLE) Cells: An in vitro lung model? K. Ridd; K. Ridd 1School of Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF Search for other works by this author on: This Site PubMed Google Scholar D. J. Alexander; D. J. Alexander 2Glaxo Wellcome, Ware, Hertfordshire, SG12 0DP Search for other works by this author on: This Site PubMed Google Scholar C. J. Reed C. J. Reed 1School of Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2000) 28 (5): A438. https://doi.org/10.1042/bst028a438a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation K. Ridd, D. J. Alexander, C. J. Reed; Foetal Rat Lung Epithelial (FRLE) Cells: An in vitro lung model?. Biochem Soc Trans 1 October 2000; 28 (5): A438. doi: https://doi.org/10.1042/bst028a438a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2000 Biochemical Society2000 Article PDF first page preview Close Modal You do not currently have access to this content.