Abstract
Perfluorochemicals (Fluosol-43) are characterized by their small size and high propensity for carrying oxygen and carbon dioxide, and also have the ability of improving the cerebral microcirculation. This study was undertaken to identify the combined effect of perfluorochemicals and irradiation in a rat brain tumor model. Brain tumors were induced by intracerebral implantation of 9L rat glioma cells (7×105 cells) into male CD Fisher 344 rats, weighing about 100 g.
To test the possibility of enhancing superoxide radical (O2‾) toxicity by Fluosol-43 treatment, tumor-bearing rats were treated with the drug diethyldithiocarbamate (DDC), an inhibitor of superoxide dismutase (SOD) which eliminates the 02‾ radical in cells. After 1 hour of intraperitoneal infusion of 1 gkg DDC, the SOD activity in the brain and brain tumor decreased to 48% and 79% of that of the controls respectively. The tumor-bearing rats were randomly divided into 4 groups; control, DDC alone, DDC with oxygen, and DDC plus Fluosol-43 with oxygen. The tumors of the control animals had a mean colony forming efficiency of 18.3±5.8 (SD) %. The mean colony forming efficiency of DDC alone, DDC with oxygen, and DDC plus Fluosol-43 with oxygen treated tumors was 13.4±4.2%, 10.5±4.9%, and 5.2±4.3% recpectively. Tumor-bearing rats were randomly divided into 6 groups; control, Fluosol-43 with oxygen, radiation alone (1, 500 rads), radiation with oxygen, Fluosol-43 plus radiation, and Fluosol-43 plus radiation with oxygen. The control animals has a mean survival time of 14.2±1.3 (SD) days and the Fluosol-43 with oxygen group showed no prolongation of the mean survival time. The radiation alone, radiation with oxygen, and Fluosol-43 plus radiation groups prolonged the mean survival time to 16.1±2.3 days, 15.6±1.6 days, and 15.5±2.3 days respectively (P<0.01) . The Fluosol-43 plus radiation with oxygen group showed a mean survival time of 19.8±2.4 days, which was significantly longer than that of the radiation with oxygen group (P<0.01).
Perfluorochemicals (Fluosol-43) with oxygen may have a synergistic effect on the radiation therapy for malignant brain tumor. Fluosol-43 with oxygen might have oxygenated the hypoxic cells to make them sensitized to radiation.
