ASSESSMENT OF QUANTITATIVE DUAL-PARAMETER FLOW CYTOMETRIC ANALYSIS FOR THE EVALUATION OF TESTICULAR TOXICITY USING CYCLOPHOSPHAMIDE -AND ETHINYLESTRADIOL- TREATED RATS
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概要
- 論文の詳細を見る
In the drug discovery process, effects to the human spermatogenesis must be fully evaluated before the first human trial. To estimate testicular toxicity, histopathological evaluation has been recommended in addition to the traditional mating procedure. However, it is laborious and time-consuming. Flow cytometric analysis (FCM) has also been applied to estimate testicular toxicity because of its speed, simplicity, and the objectivity of the data. Using cyclophosphamide (CP)- and ethinylestradiol (EE)-treated rat testis, we attempted to validate our dual-parameter, DNA ploidy and cell-size FCM, in a high-throughput toxicity study. Our results showed that CP damaged some spermatogonia and some early meiotic spermatocytes and EE caused severe decrease of spermatogenic cells except for spermatogonia as well as marked decrease of somatic cells, most probably Leydig cells. This is the first report discriminating between the changes of spermatogonia and that of somatic cells with ECM analysis. These results demonstrate that this method is a very useful and powerful tool to assess testicular toxicity, especially in high-throughput toxicological studies.
- 日本トキシコロジー学会の論文
- 2002-05-17
著者
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INOUE Tohru
Safety and Research Center of National Institute of Health Sciences
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Kitajima Satoshi
Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health
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Satoh Kanako
東京都健康安全研究センター 環境保健部
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KATOH CHIAKI
Department of Internal Medicine, National Hospital Organization Nagoya Medical Center
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Shirao Kuniaki
Gastrointestinal Oncology Division National Cancer Center Hospital
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Sai Kimie
Divislon Of Toxicology National Institute Of Health Sciences
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Sai-kato Kimie
Division Of Toxicology
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Sekita Kiyoshi
Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences
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INOUE Tohru
Center for Biological Safety and Research
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KITAJIMA Satoshi
Cellular & Molecular Toxicology Division, Biological Safety Research Center, National Institute of H
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INOUE Tohru
Cellular & Molecular Toxicology Division, Biological Safety Research Center, National Institute of H
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KANNO Jun
Cellular & Molecular Toxicology Division, Biological Safety Research Center, National Institute of H
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Horii Ikuo
Department of Toxicology and Pathology, Nippon Roche K.K.Research Center
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Horii I
Drug Safety Research And Development Pfizer Global Research And Development Nagoya Laboratories. Pfi
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Kanno Jun
Division Of Molecular Toxicology National Institute Of Health Sciences
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Horii Ikuo
Department Of Preclinical Science Nippon Roche K. K. Research Center
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Katoh C
Nippon Roche K. K. Kanagawa Jpn
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Katoh Chiaki
Department Of Preclinical Science Nippon Roche K. K. Research Center
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Inoue T
Nippon Roche Res. Center Kanagawa Jpn
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SAGA Yumiko
Cellular and Molecular Toxicology Division, Biological Safety Research Center
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Sakemi Kazue
Division Of Pharmacology And Biological Safety Research Center National Institute Of Health Sciences
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Saga Yumiko
Division Of Mammalian Development National Institute Of Genetics
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Saga Yumiko
Dept. Op Toxicology Biological Safety Research Center Nihs
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Horii Ikuo
Worldwide Safety Sciences Pgrd Nagoya Laboratories Pfizer Inc.
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Kitajima S
Department Of Environmental Health And Toxicology Tokyo Metropolitan Institute Of Public Health
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Kanno Jun
国立医薬品食品衛生研究所安全性生物試験研究センター
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Kanno Jun
Cel. Mol. Tox. Div. Nihs
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Inoue Tohru
New Business Development Biacore K. K.
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Saga Yumiko
Div. Of Mammalian Dev. National Inst. Of Genetics
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Horii Ikuo
Department Of Biochemical Toxicology School Of Pharmacy Showa University
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