このエントリーをはてなブックマークに追加
ID 37862
本文ファイル
著者
Saeki, Shuji
Nishiyama, Masahiko
Toge, Tetsuya
キーワード
DT-diaphorase
Mitomycin C
Biochemical modulation
Microenvironmental pH
NDC
医学
抄録(英)
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.
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.
掲載誌名
Hiroshima Journal of Medical Sciences
44巻
3号
開始ページ
55
終了ページ
63
出版年月日
1995-09
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
他の一覧