A radiometric method for evaluation of chemotherapy sensitivity: results of screening a panel of human breast cancer cell lines.

We have used a radiometric method to screen for chemotherapy sensitivity among a panel of human breast cancer cell lines. This method utilizes the inhibition of conversion of [14C]glucose to 14CO2 as an index of cytotoxicity. Nine different breast cancer cell lines were exposed for 1 h to 4 different concentrations of several antineoplastic agents with and without documented clinical activity against breast cancer. Cytotoxic effects were analyzed as a function of the ratio of the concentration required to inhibit cell growth to 50% of control to 1/10 of the known peak plasma concentration in humans for each particular drug. The drug-induced inhibition of 14C production by breast cancer tumor cells correlated strongly with the drug-induced antiproliferative effect (P less than 0.002) and with the inhibition of colony formation in a soft agar cloning assay (P less than 0.05). The HS578T cell line and one of the MCF7 cell lines exhibited a chemosensitivity pattern consistent with the clinical responsiveness of human breast cancer to the agents tested. Most of the other cell lines exhibited resistance to clinically active agents, especially the cell lines obtained from patients exposed to prior chemotherapy. These results suggest that this radiometric method measures a drug-induced metabolic effect that correlates with the antiproliferative activity of antineoplastic agents on breast cancer cells. The HS578T and the MCF7-KO cell lines, tested in this system, could be a useful screen for new anticancer compounds with activity against human breast cancer.