[Effect of perfluorochemicals on BCNU chemotherapy in a rat brain-tumor model]

Perfluorochemicals (Fluosol-43) is characterized with its small size and high propensity for carrying oxygen and carbon dioxide, and also have the function to improve the cerebral microcirculation. These characteristic features of Fluosol-43 may have a beneficial effect on brain-tumor chemotherapy in terms of the oxygenation of hypoxic cells, and/or the improvement of the pharmacokinetics of anticancer drugs. This study was undertaken to identify the combined effect of perfluorochemicals (Fluosol-43, 20 ml/kg) and chemotherapeutic agent (BCNU, LD10 dose; 13.3 mg/kg) in a rat brain-tumor model. Brain-tumor model was made by the intracerebral implantation of C6 rat glioma cells (1 X 10(5) cells/10 microliters). At 10 days after implantation, control animals had a macrotumor weighing about 100 mg with large part of central necrosis. The tumor-bearing rats for 10 days after implantation were randomly divided into 4 groups; a control group, a Fluosol-43 treatment group, a BCNU treatment group, and a Fluosol-43 plus BCNU treatment group. Control animals had mean survival time of 19.94 +/- 2.41 (S.D.) days, and mean survival time of Fluosol-43 treatment group was 19.47 +/- 1.36 days. BCNU treatment alone prolonged the mean survival time to 28.36 +/- 7.94 days (p less than 0.001). Fluosol-43 plus BCNU treatment group showed 36.00 +/- 10.15 days, which was significantly greater than that of BCNU treatment alone group (p less than 0.005). The long survivals lived over 50 days after implantation were 7 out of 27 rats in Fluosol-43 plus BCNU treatment group, in contrast to one out of 25 rats in BCNU treatment alone group. Perfluorochemicals (Fluosol-43) may have the synergistic effect on BCNU chemotherapy for brain tumors. It was speculated for the above results that following the oxygenation of hypoxic cells by Fluosol-43, hypoxic cells might be sensitized to BCNU, which might be much delivered into hypoxic area. And further studies should be done for the evaluation of the mechanism of perfluorochemicals on brain tumor experimentally before clinical application.