Biophysical aspects of the integrated combination of cytostatic drugs with radiotherapy. Part 2: Dose-effect relationships and 31P NMR spectroscopy of L 1210 cells (monolayers) and 9L glioma cells (monolayers and tumor spheroids) treated with activated isophosphamide, adriamycin, epirubicin and 6 MeV electrons.

Dose-effect relations have been evaluated by the treatment of cell cultures (9L glioma cells of rat as monolayers and tumor spheroids, L 1210 cells of mice) with activated isophosphamide, adriamycin, epirubicin and 6 MeV electrons. The magnitude of synergistic effects obtained by combined treatment modalities is strictly pH-dependent, but even for tumor spheroids it appears that there exists an optimum time-interval between drug administration and consecutive irradiation. The determination of the intracellular pH value with the help of pH sensor microelectrodes and 31P NMR spectroscopy indicates that 31P spectroscopy only provides the global pH of the complete culture (average value), whereas the local pH can only be determined by sensors. The ATP-concentration before and after irradiation depends significantly on the glucose supply of the culture medium.