Reevaluation of the Radiosensitizing Effects of Sanazole and Nimorazole In Vitro and In Vivo
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- SUGIE Chikao
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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- SHIBAMOTO Yuta
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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- ITO Masato
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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- OGINO Hiroyuki
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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- SUZUKI Hiromasa
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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- UTO Yoshihiro
- Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
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- NAGASAWA Hideko
- Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
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- HORI Hitoshi
- Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima
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抄録
Sanazole (AK-2123, 3-nitrotriazole derivative, N1-(3-methoxypropyl)-2-(3-nitro-1 H-1,2,4-triazol-1-yl)acetamide) and nimorazole (5-nitroimidazole derivative, 4-(2-(5-nitro-1H-1-imidazolyl)ethyl)morpholine) have been tested clinically as hypoxic cell radiosensitizers, mainly outside Japan. To determine if these sensitizers deserve clinical investigation in Japan, we reevaluated the radiosensitizing effects of these compounds in vitro and in vivo, in comparison with a fluorinated 2-nitroimidazole derivative KU-2285 (N1-(2-hydroxyethyl)-1,2-difluoro-3-(2-nitro-1 H-1-midazolyl)propanamide). KU-2285 is a known and established radiosensitizer, but is not suitable for clinical studies because of the high cost of synthesis. In vitro, the radiosensitizing effects of the three compounds on SCCVII (squamous cell carcinoma line in C3H mice) tumor cells were examined at 0.5 and 1 mM under aerobic or hypoxic conditions, using a colony assay. In vivo, SCCVII tumors grown subcutaneously in the hind legs of C3H/HeN mice were irradiated with or without prior intraperitoneal administration of 100, 200 or 400 mg/kg of the drugs. Thereafter, tumor growth delay was measured. In vitro, no sensitizing effect was observed under aerobic conditions at 1 mM. Under hypoxic conditions, the sensitizer enhancement ratio (SER) determined at 1% cell survival level for sanazole, nimorazole and KU-2285 was 1.55, 1.45 and 1.95, respectively, at 1 mM, and 1.40, 1.40 and 1.75, respectively, at 0.5 mM. In vivo, all three compounds had significant radiosensitizing effects; their effects appeared to decrease in the order of KU-2285, sanazole, and nimorazole. It was suggested that sanazole may be more suitable for clinical trials than nimorazole.<br>
収録刊行物
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- Journal of Radiation Research
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Journal of Radiation Research 46 (4), 453-459, 2005
Journal of Radiation Research 編集委員会
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詳細情報 詳細情報について
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- CRID
- 1390001205217647104
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- NII論文ID
- 110004061521
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- NII書誌ID
- AA00705792
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- ISSN
- 13499157
- 04493060
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- NDL書誌ID
- 7752035
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- NDL-Digital
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可