Inability of a human lung tumour cell line (A549) to detect chemically induced organ-specific toxicity to the lung

Abstract

In this study the potential of a human lung tumour cell line to detect organ-specific toxicity to the lung was assessed and several methods of estimating cytotoxicity were evaluated. Three known pulmonary toxins, bleomycin, butylated hydroxytoluene (BHT) and paraquat, were studied for their effects on a human lung tumour cell line (A549). The effect of diquat, a compound structurally similar to paraquat but not toxic to the lung, was also investigated. Cytotoxicity was assessed by measuring the effects of the chemicals on protein synthesis, vital dye exclusion, cell numbers and clonogenicity. The sensitivity of these methods varied considerably. For all the compounds evaluated, the clonogenic assay was by far the most sensitive indicator of toxicity. The IC 50 value for bleomycin was more than 10,000 times higher when assessed by trypan blue exclusion or by inhibition of protein synthesis than by the clonogenic assay. Results show that the A549 cell line, derived from an alveolar epithelial cell, is a poor model for organ-specific toxicity as it does not distinguish between paraquat and diquat. If a cell line is to be of value in studying organ-specific toxicity, it must retain those differentiated functions that are involved in the mechanisms of toxicity of the chemicals under investigation. These data highlight the difficulty of using in vitro cell lines to predict in vivo toxicity to the lungs.