IN-VITRO CYTOTOXICITY TESTING OF POTENTIALLY ACTIVE ANTI-HIV DRUGS WITH CULTURED-CELLS

This study compared the ability of two continuous cell lines to predic t the cytotoxicity of potentially active anti-HIV drugs. Human fetal l ung fibroblasts (HFL1) and CD4(+) T-lymphocytes (CEM-IW) were incubate d in the absence or presence of increasing concentrations of 12 antivi ral compounds. These six-membered unsaturated nucleoside analogues wer e stereospecifically synthesised in our laboratories, and were evaluat ed for cytotoxicity as well as for antiviral activity. Cells were incu bated for six days and mitochondrial activity (XTT and MTT assays) was used to assess cytotoxicity. IC50 values were derived from concentrat ion-effect curves after linear regression analysis. Comparison of the two sets of cytotoxicity data suggests that the experimental IC50 valu es from HFL1 cells correlate well with the values obtained in lymphocy te studies performed at the National Cancer Institute laboratories (r value = 0.93). For the 12 antiviral chemicals, and those we have teste d previously, these methods probably detect basal cytotoxicity, i.e. t he toxicity of a chemical to basic cellular functions and structures c ommon to all mammalian specialised cells. However, as with any testing procedure, some chemicals may elude the cytotoxicity screen, as a res ult of false negatives due to solubility, miscibility and organ-specif ic effects, and could be mislabelled as having low toxic potential. It is therefore conceivable that tests involving continuous differentiat ed cell lines of various origins could be developed to cover a large p ercentage of toxic effects, thereby reducing the need to introduce man y laborious assay systems with freshly-isolated primary cultures.