ENHANCEMENT OF MITOMYCIN C UPTAKE BY ISOPROTERENOL IN RAT ASCITES HEPATOMA
スポンサーリンク
概要
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The amounts of mitomycin C (MMC) taken up into rat ascites hepatoma cells were determined by measuring the decrease in the absorbance of the incubation medium at 363 nm. The extracellular concentration of MMC decreased progressively in AH130 cell suspension and no peaks other than MMC were detected by analytical high-performance liquid chromatography (HPLC). Isoproterenol (IPN) enhanced the uptake of MMC into AH44 and AH130 cells but not AH13 cells in which the uptake increased by N^6,O^<2'>-dibutyryl cyclic adenosine 3' : 5'-monophosphate (dibutyryl cyclic AMP). The increase of uptake of MMC by IPN was inhibited by propranolol and the uptake of MMC increased in a dose-dependent manner by theophylline in AH130 cells. The maximum combined cytotoxicity was observed when AH130 cells were treated with IPN at 10^<-7> M for 30 min before the exposure to MMC and, in this pretreatment condition, the uptake of MMC was enhanced in parallel with the increase of cyclic adenosine 3' : 5'-monophosphate (cyclic AMP) level in the cells. On the other hand, MMC, which had no stimulating effect on the intracellular cyclic AMP level, nevertheless maintained a high level of intracellular cyclic AMP elevated by IPN for a longer period than in the treatment with IPN alone and prolonged the period of acceleration of the uptake of MMC. In the in vivo combined treatment with IPN and MMC, the life span of AH44-bearing rats was prolonged and 2 out of 6 rats were cured, while the mean survival time of the rats treated with MMC alone was 11.3 d. These results indicated that the intracellular cyclic AMP, which is maintained at a high concentration for a long period by the combined action of IPN and MMC, enhanced the uptake and the antitumor effect of MMC.
- 公益社団法人日本薬学会の論文
著者
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MIYAMOTO Kenichi
Department of Medical Genetics, Ehime University School of Medicine
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MIYAMOTO Kenichi
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University
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WAKI Yoshihiro
Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kan
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Miyamoto Kenichi
Department Of Hospital Pharmacy And Department Of Medicinal Informatics Graduate School Of Medical S
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Matsunaga Takayuki
Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un
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Waki Yoshihiro
Department Of Pharmacology And Pharmaceutics Graduate School Of Natural Science And Technology Kanaz
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Waki Yoshihiro
Department Of Pharmacology Hokuriku University School Of Pharmacy
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Koshiura Ryozo
Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar
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MATSUNAGA TAKAYUKI
Department of Pharmacology, Hokuriku University School of Pharmacy
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KOSHIURA RYOZO
Department of Pharmacology, Hokuriku University School of Pharmacy
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Miyamoto K
Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University
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Koshiura R
Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar
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Miyamoto K
Department Of Engineering Physics And Mechanics Kyoto University
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Miyamoto Kenichi
Department Of Chemistry For Materials Faculty Of Engineering And Graduate School Of Engineering Mie
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MIYAMOTO Kenichi
Department of Engineering Physics and Mechanics, Kyoto University
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