Preliminary Investigations into the use of a Human Bronchial Cell Line (16HBE14o-) to Screen for Respiratory Toxins In Vitro.
A transformed epithelial cell line derived from normal human bronchial epithelium (16HBE14o- cells) was used to assess the in vitro toxicity of six compounds. The compounds were sodium chloride and titanium dioxide (reference compounds) and sodium carbonate and silica (respiratory toxins). In addition, two compounds (compounds A and B) were tested which have been shown to induce respiratory toxicity in the rat during preclinical safety assessment. Confluent monolayers of 16HBE14o- cells were treated for 24hr with the test compounds and toxicity was assessed using two conventional cytotoxicity assays (neutral red uptake and MTT reduction). Transepithelial resistance (TER) was also measured throughout the treatment period as a possible alternative endpoint for toxicity measurement. Neither sodium chloride nor titanium dioxide caused toxicity in 16HBE14o- cells using any of the toxicity endpoints. With the exception of silica, all irritant compounds caused concentration-related cytotoxicity in 16HBE14o- cells. For each compound, when the three toxicity endpoints were compared, similar IC(50) values were obtained irrespective of the endpoint used. These initial results indicate that 16HBE14o- cells may be a suitable cell line for future use in development of in vitro assays for respiratory toxicity.
Westmoreland
C
C
Strategic Toxicological Sciences, GlaxoWellcome Research and Development, Park Road, Ware, Herts SG12 0DPRespiratory Diseases, GlaxoWellcome Research and Development, Stevenage, Herts SG1 2NY, UK.
Walker
T
T
Matthews
J
J
Murdock
J
J