In vitro cytotoxicity testing of potentially active anti-HIV drugs with cultured cells

By Hopkinson, D. - Scheiner, P. - Barile, F.A.

This study compared the ability of two continuous cell lines to predict the cytotoxicity of potentially active anti-HIV drugs. Human fetal lung fibroblasts (HFL1) and CD4+ T-lymphocytes (CEM-IW) were incubated in the absence or presence of increasing concentrations of 12 antiviral compounds. These six-membered unsaturated nucleoside analogues were stereospecifically synthesised in our laboratories, and were evaluated for cytotoxicity as well as for antiviral activity. Cells were incubated for six days and mitochondrial activity (XTT and MTT assays) was used to assess cytotoxicity. IC50 values were derived from concentration-effect curves after linear regression analysis. Comparison of the two sets of cytotoxicity data suggests that the experimental IC50 values from HFL1 cells correlate well with the values obtained in lymphocyte studies performed at the National Cancer Institute laboratories (r value =0.93). For the 12 antiviral chemicals, and those we have tested previously, these methods probably detect basal cytotoxicity, i.e. the toxicity of a chemical to basic cellular functions and structures common to all mammalian specialised cells. However, as with any testing procedure, some chemicals may elude the cytotoxicity screen, as a result of false negatives due to solubility, miscibility and organ-specific effects, and could be mislabelled as having low toxic potential. It is therefore conceivable that tests involving continuous differentiated cell lines of various origins could be developed to cover a large percentage of toxic effects, thereby reducing the need to introduce many laborious assay systems with freshly-isolated primary cultures.