IN VITRO RADIO-AND THERMALSENSITIZATION BY (-)-(R)-2-AMINOMETHYLPYRROLIDINE (1, 1-CYCLOBUTANEDICARBOXYLATO) PLATINUM (II) MONOHYDRATE (DWA2114R)

Radio and thermal sensitization effects on in vitro cultured mammalian cells of (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinuth (II) monohydrate (DWA2114R) were investigated. Radiosensitization by DWA2114R was more pronounced in hypoxic cells than in aerobic cells. Dose modifying factors (DMF) in hypoxic V 79 cells was about 1.3 at 100μM and 300μM DWA2114R during gamma-ray irradiation. DMF in aerobic cells was 1.06 at 300μM. At elevated temperature, the cytotoxicity of DWA2114R was enhanced in FM 3 A cells. DMF for cell killing at 10μM DWA2114R was 5.77 at 42°C, 1.71 at 43°C and 1.59 at 44°C. The activation energy in the presence of DWA2114R between 42°C and 44°C was comparable to that in the absence of drug between 43 and 44°C. Enhanced cytotoxicity of DWA2114R depended on the sequence of drug and heat. Enhanced killing was observed when the drug was administered either during or immediately after heat. Present results suggest that the combined DWA2114R and heat or radiation may improve the therapeutic ratio in thermal-or radio-chemotherapy.