MICROCALORIMETRIC EVALUATION OF THE EFFECT OF COMBINED CHEMOTHERAPEUTIC DRUGS

A study of the effect of combined antineoplastic drugs in vitro was ca rried out by microcalorimetric monitoring of the metabolic activity of treated cells. Power-time curves of growing T-lymphoma cell suspensio ns, treated with single or combined drugs, were recorded. The extent o f the effect was evaluated by changes in the slopes of the microcalori metric curves and the kinetics of the drug action were interpreted fro m the time at which these changes reached their maximum value. The met hod was validated using two well-established drug combinations, the po tentiatory effect of dipyridamole on methotrexate cytotoxicity, and th e synergism between methotrexate and 6-thioguanine. In the first case, where one drug is not toxic, the modulation may be evaluated by compa ring the inhibition produced by the toxic drug alone and in combinatio n with its modulator. Otherwise, when both drugs are toxic, the combin ed effect must be evaluated by means of their combination index. The m easurement procedure is simple, the electric signal is well suited to automation of data acquisition and the response may be evaluated withi n 5 to 6 h of drug administration. Moreover, we demonstrate that micro calorimetry is a reliable method for the detection of modulatory effec ts in combination chemotherapy.