THE EFFECT OF DEXAMETHASONE ON THE UPTAKE OF CISPLATIN IN 9L GLIOMA AND THE AREA OF BRAIN AROUND TUMOR

The negative influence of dexamethasone (Dex) on the uptake of cisplat in in brain tumors was investigated in rats bearing 9L glioma. Dex or saline was given intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total Platinum (Pt) concentration was quantifie d with atomic absorption spectroscopy (AAS) in tumor, brain around tum or (BAT), normal brain and plasma. In the second experiment DNA-adduct s of cisplatin were determined in tumor and BAT by AAS. In tumor, ther e. was no difference in the Pt concentration and in the DNA-adduct lev el between the two treatment groups. In BAT, the Pt level in the Dex g roup was 0.20 mu g/g (SD = 0.10 mu g/g), which was significantly lower than in the controls (0.53 mu g/g (SD = 0.21 mu g/g); p < 0.001). In addition? the DNA-adduct level in BAT was 23% lower in the Dex treated rats (p = 0.05). In normal brain the Pt concentration was 10-fold low er than in tumor tissue. Thus, Dex did not significantly limit the upt ake of cisplatin in brain tumor nor did it influence th uptake in norm al brain parenchyma. In contrast, in BAT that has a partially disrupte d BBB, the concentrations of Pt and DNA-adduct formation were signific antly decreased following pretreatment with Dex. The influence of Dex on limiting the effects of chemotherapy for brain tumors needs further study.