Use of a radiometric system to screen for antineoplastic agents: correlation with a human tumor cloning system

A rapid, semiautomated radiometric system is described for screening for new antineoplastic agents. This radiometric system utilizes inhibition of conversion of [14C]glucose to 14CO2 as an index of cytotoxicity. In this study the radiometric system (BACTEC 460) was first optimized using a variety of human and animal tumor cell lines. Overall, there was a clear linear relationship between the number of cells seeded and the production of 14CO2 from [14C]glucose. The BACTEC System easily detected antitumor activity of compounds from all four classes of antineoplastic agents (doxorubicin, vinblastine, cis-platinum, and methotrexate.) Human tumor cell lines were used to compare the antitumor activity of the same four agents measured by the BACTEC System versus the antitumor activity of the same agents measured by a conventional cloning system. For all cell lines tested there was good agreement in comparison of percentage of survival measured by the BACTEC System versus the standard cloning system. This agreement was better for a continuous exposure to drug in both systems (r = 87, P = less than 0.001) than for a 1-h exposure to the drug (r = 0.35, P = 0.036). In addition to determining the effect of drugs on tumor cells, the BACTEC System was successfully utilized to determine the cytotoxic effect on normal bone marrow buffy coat cells. By utilizing a comparison of suppression of 14CO2 production by normal versus tumor cells, a measurement of differential cytotoxicity could be made. Based on these findings, the radiometric BACTEC System represents a simple and rapid method to detect cytostatic or cytocidal activity of new compounds. It is ideal for use as a prescreen for testing a large number of new chemical entities against a large number of human tumor cell lines.