NUCLEAR BINDING AS A DETERMINANT OF TISSUE DISTRIBUTION OF ADRIAMYCIN, DAUNOMYCIN, ADRIAMYCINOL, DAUNORUBICINOL AND ACTINOMYCIN D
スポンサーリンク
概要
- 論文の詳細を見る
The tissue distribution mechanism of adriamycin (ADR), its relatives, daunomycin (DNR), adriamycinol (ADR-ol), daunorubicinol (DNR-ol) and actinomycin D (ACT-D) has been studied in rats and rabbits. The following evidences with respect to tissue dustribution of ADR were obtained : 1) remarkable binding of ADR to tissue homogenate, 2) significant difference in the tissue binding of ADR among tissues, 3) exclusive localization of ADR in cell nucleus, 4) good correlation between the tissue binding of ADR and the tissue desoxyribonucleic acid (DNA) concentration, 5) comparatively good coincidence between the experimentally determined tissue binding of ADR and that calculated from in vitro nuclear binding parameters reported and the tissue DNA concentration, and 6) no correlation between the concentration of tissue phospholipids (i.e. cardiolipin, acidic phospholipids and total phospholipids) and the K_p value of ADR in rats. From these findings, it was confirmed that the nuclear binding is a determinant of the extensive tissue distribution of ADR and that a remarkable variation in the tissue concentration of ADR is due mainly to the difference in the tissue DNA concentration. Furthermore, good correlations were demonstrated between the DNA concentration and Kp_<app> values of DNR and ACT-D in rats and DNR, ADR-ol and DNR-ol in rabbits. Hence, it is suggested that there is a common mechanism of in vivo tissue distribution of ADR and its relatives which can intercalate to DNA and the determinant of characteristic tissue distribution is nuclear binding of these antibiotics.
著者
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TERASAKI Tetsuya
Faculty of Pharmaceutical Sciences, Kanazawa University
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Sawada Yasufumi
Faculty Of Pharmaceutical Sciences Tokushima Bunri University:faculty Of Pharmaceutical Sciences Uni
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HANANO Manabu
Faculty of Pharmaceutical Sciences, University of Tokyo
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SUGIYAMA Yuichi
Faculty of Pharmaceutical Sciences, University of Tokyo
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IGA Tatsuji
Faculty of Pharmaceutical Sciences, University of Tokyo
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Terasaki Tetsuya
Faculty Of Pharmaceutical Sciences Kanazawa University
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Terasaki Tetsuya
Faculty Of Pharmacutical Sciences University Of Tokyo (present Address) Faculty Of Pharmaceutical Sc
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Hanano M
Department Of Pharmaceutics College Of Pharmacy Nihon University
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Hanano Manabu
Faculty Of Pharmaceutical Science University Of Tokyo
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Sugiyama Yuichi
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Iga Tatsuji
Faculty Of Pharmaceutical Sciences University Of Tokyo
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Sugiyama Yuichi
Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Iga Tatsuji
Division Of Gastroenterology Department Of Medicine Kurume University School Of Medicine
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