悪性脳腫瘍における5-FU選択的腫瘍到達性増強法の検討
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概要
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We investigated the enhancement effects of 5-FU into maligant glioma with an addition to uracil in vitro, and in vivo. Glioma bearing rats were made by intracerebral inoculation of RG 12 tumor cells, which were established from nitrosourea-induced rat glioma, stereotaxically. Histologically this tumor showed massive central necrosis, pleocytosis, and many mitosis, which seemed to be similar to the findings of human malignat gliomas. In 3 weeks after intracerebral inoculation of tumor cells, rats were orally taken with FT only or FT plus uracil (molar ratio 1 : 4) and seriously sacrified, then FT and 5-FU concentrations of brain tumors, normal brain tissue, blood, and liver, which was a main site of the metabolism of 5-FU, were measured using chemical assay technique. FT concentration in blood declined in both groups as time lapsed, and plasma half-time was 3.5 hour in FT only and 6.4 hour in another group. Concentration of 5-FU in blood was kept constant in low level. In brain tumors significant high level of 5-FU after the administration of FT plus uracil was found as compared with that after the administration of FT only. In liver tissue similar results were demonstrated, too. The absorption from small intestine and distribution of FT were influenced more and faster by an addition to uracil because area under curve (AUC) increased and Tpeak shortened. Besides in vitro, significant active conversion from FT to 5-FU in RG 12 cells was also shown. From these results and relevant literatures, the mechanism of enhanced attainability to brain tumor of 5-FU using the combination of FT and uracil was dsicussed.
- 神戸大学の論文