A NONCLONOGENIC CYTOTOXICITY ASSAY USING PRIMARY CULTURES OF PATIENT TUMOR-CELLS FOR ANTICANCER DRUG SCREENING

Primary cultures of cells from patients with chronic lymphocytic leuke mia (CLL) and ovarian carcinoma (Ovca) were compared with the renal ca rcinoma ACHN and the lymphocytic CCRF-CEM human tumor cell lines in re sponse to 63 toxic or nontoxic compounds. The experiments were conduct ed at 1, 10, and 100 mu g/ml in 96-well microtiter plates for an assay time of 72 h. The plates were analyzed by the fully automated Dynatec h Immune Assay System (DIAS) using Alamar blue as a fluorometric/color imetric indicator of metabolic activity. Drug response data were repor ted as the area under the tumor cell survival-concentration curve (AUC ). Noncytotoxic compounds were classified as inactive by all cell syst ems. According to the AUG, CCRF-CEM and CLL cells were the most sensit ive, followed by ACHN, and then Ovca, Many of the clinically active dr ugs were detected by all cell systems. However, the sensitivity patter n differed considerably between the cell types as judged from correlat ion analysis, and a higher proportion of clinically inactive drugs wer e scored as active by the cell lines compared with the primary culture s. Ovca showed the highest ratio of clinically solid tumor active/clin ically inactive agents followed by CLL. The results indicate that prim ary cultures of human tumor cells may be a useful and valuable model f or anticancer drug screening.