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DT-diaphorase as a Target Enzyme for Biochemical Modulation of Mitomycin C
https://hiroshima.repo.nii.ac.jp/records/2013369
https://hiroshima.repo.nii.ac.jp/records/2013369af12af84-f048-4d31-8212-9cac9baf9c17
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
HiroshimaJMedSci_44_55.pdf (898.3 KB)
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| Item type | デフォルトアイテムタイプ_（フル）(1) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2023-03-18 | |||||||||||
| タイトル | ||||||||||||
| タイトル | DT-diaphorase as a Target Enzyme for Biochemical Modulation of Mitomycin C | |||||||||||
| 言語 | en | |||||||||||
| 作成者 |
Saeki, Shuji
× Saeki, Shuji
× Nishiyama, Masahiko
× Toge, Tetsuya
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| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 主題 | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | DT-diaphorase | |||||||||||
| 主題 | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Mitomycin C | |||||||||||
| 主題 | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Biochemical modulation | |||||||||||
| 主題 | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Microenvironmental pH | |||||||||||
| 主題 | ||||||||||||
| 主題Scheme | NDC | |||||||||||
| 主題 | 490 | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述 | We studied a selective enhancement of the mitomycin C (MMC)-induced antitumor effect focusing on the intracellular metabolism by NAD(P)H:quinone oxidoreductase (DT-diaphorase, DTD). The level of cellular DTD activity related well to the degree of MMC-induced DNA total cross links and cell growth inhibition in human cancer cell lines, KB, PH101, SH101 and K562. A DTD inhibitor, dicoumarol (DIC) or flavin adenine dinucleotide (FAD), inhibited the MMC-induced DNA damage and cytotoxicity at a non-toxic concentration. The DTD-mediated MMC activation was pH-dependent, and highest at pH 6 and lowest at pH 8. Although an inverse relationship appeared to exist between DTD activity and MMC efficacy in human xenografts implanted into nude mice and 9 fresh human tumor specimens, the investigation in 3 culture cells, HEC-46, HCC-48 and HCC-50, established from those xenografts, showed that DTD activated MMC in a pH-dependent manner as well as the other cell lines. Significant tumor pH reduction from 7.1 to 6.7 by continuous glucose infusion also increased the MMC-induced tumor growth inhibition in the human tumor xenografts. Thus, we conclude that bioreductive activation by DTD in a pH-dependent manner may be of key importance in the MMC-induced antitumor effect and that an increased MMC efficacy at a reduced pH caused by hyperglycemia may be applied to clinical use as a new manipulation for a biochemical modulation of MMC. | |||||||||||
| 言語 | en | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | This work was presented in part at the 40th Annual Meeting of Japan Soc. for Chemotherapy, Nagoya, 1992, the 18th International Congress of Chemotherapy, Stockholm, 1993 and the 52nd Annual Meeting of Japan Cancer Assoc., Sendai, 1993. | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | Hiroshima University Medical Press | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||
| 資源タイプ | departmental bulletin paper | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 収録物識別子 | ||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||
| 収録物識別子 | 0018-2052 | |||||||||||
| 収録物識別子 | ||||||||||||
| 収録物識別子タイプ | NCID | |||||||||||
| 収録物識別子 | AA00664312 | |||||||||||
| 開始ページ | ||||||||||||
| 開始ページ | 55 | |||||||||||
| 書誌情報 |
Hiroshima Journal of Medical Sciences Hiroshima Journal of Medical Sciences 巻 44, 号 3, p. 55-63, 発行日 1995-09 |
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| 旧ID | 37862 | |||||||||||
