Foetal rat lung epithelial (FRLE) cells: partial characterisation and response to pneumotoxins.
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.
Ridd
K
K
School of Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK. kr47@le.ac.uk
Alexander
D J
DJ
Reed
C J
CJ
D000818:Animals; D001969:Bromobenzenes / Q000009:adverse effects; D019256:Cadmium Chloride / Q000009:adverse effects; D002460:Cell Line; D003035:Cobalt / Q000009:adverse effects; D003603:Cytotoxins / Q000009:adverse effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005333:Fetus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D017403:In Situ Hybridization; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009281:Naphthalenes / Q000009:adverse effects / Q000737:chemistry; D009499:Neutral Red / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity; D009582:Nitrofurantoin / Q000009:adverse effects; D010269:Paraquat / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger; D051381:Rats
D001969:Bromobenzenes; D003603:Cytotoxins; D009281:Naphthalenes; D009574:Nitro Compounds; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D009499:Neutral Red; D003035:Cobalt; D007633:Keratins; D009582:Nitrofurantoin; D006861:Hydrogen Peroxide; C032036:bromobenzene; C018021:cobaltous chloride; D019256:Cadmium Chloride; D010269:Paraquat