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ID 37819
本文ファイル
著者
Sakamoto, Noriaki
Toge, Tetsuya
Nishiyama, Masahiko
キーワード
DT-diaphorase
NADPH cytochrome P450
Mitomycin C
Biochemical modulation
NDC
医学
抄録(英)
The bioreductive activation of mitomycin C (MMC) has been investigated using 10 human cancer cell lines. Except for 2 lines (COLO201 and COLO320DM), the cellular NAD(P)H: quinone oxidoreductase (DTD) activities correlated well with MMC-induced DNA damage and cytotoxicity. In addition, when the DTD activity was inhibited with 50 mM dicoumarol, the MMC activity decreased significantly. On the other hand, no correlation between the NADPH cytochrome P450 reductase (P450) activity and MMC efficacy was observed. We postulate that two electron reduction by DTD may be more important in MMC activation than one electron reduction by P450. The DTD-mediated metabolism was pH-dependent. In a nude mouse experimental model, the pH in the tumor decreased under hyperglycemic conditions due to unique glycolysis. The administration of m-iodobenzyl-guanidine (MIBG) enhanced the decrease in the pH of the tumor without affecting the pH of normal tissue (liver). It also significantly increased the antitumor activity of MMC. However, this biochemical modulation had no effect in the COLO201 and COLO320DM cells. Other mechanisms may be involved in the regulation of MMC activity in these cells. In conclusion, DTD may be an important target of MMC. Biochemical modulation using MIBG and glucose may selectively enhance the activity of MMC within cancer cells.
内容記述
This work was presented in part at the 95th and 96th Annual Meetings of the Japan Society for Surgery, Nagoya, 1994, and Makuhari, 1996.
掲載誌名
Hiroshima Journal of Medical Sciences
46巻
2号
開始ページ
67
終了ページ
73
出版年月日
1997-06
出版者
Hiroshima University Medical Press
ISSN
0018-2052
NCID
言語
英語
NII資源タイプ
紀要論文
広大資料タイプ
学内刊行物(紀要等)
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
publisher
部局名
原爆放射線医科学研究所
医歯薬学総合研究科
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