COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 12)EFFECTS OF CYCLOPHOSPHAMIDE ON SPERMATOGENESIS

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概要

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• To determine what is an appropriate administration period for evaluation of the testicular toxicity of cyclophosphamide, the compound was administered orally to male Crj:(CD)SD rats at doses of 5, 10, 20 and 40 mg/kg/day for 2 weeks and at doses of 2.5, 5 and lO mg/kg/day for 4 weeks. All animals in the 2-week treatment group given 40 mg/kg/day died during the treatment period. After repeated dosing, weights of testes and epididymides did not change significantly in either 2-week or 4-week treatment groups. On conventional histopathological examination, changes in spermatogonia were too subtle to allow simple quantitative evaluation. Therefore the quantitative analysis described by Matsui et al. (l995) was employed. After 4-weeks treatment all types of germ cells decreased significantly in all stages of seminiferous tubules examined in the 10 mg/kg/day group. Spermatogonia type A in all stage seminiferous tubules examined and spermatogonia type B in stage V seminiferous tubules decreased significantly in the 5 mg/kg/day group. With 2-weeks treatment, spermatogonia type A in all stage seminiferous tubules examined were similarly decreased significantly in 10 mg/kg/day or more groups. Spermatogonia type B and pachytene spermatocytes in stage V, preleptotene spermatocytes in stage VII and zygotene spermatocytes in stage Xll were decreased in 20 mg/kg/day group. Sertoli cells and the Leydig cells and epididymides were not affected in any treatment group. In conclusion, testicular toxicity induced by cyclophosphamide could be detectable after 2-weeks as well as after 4-weeks treatment if precise histopathological examination including quantitative analysis of spermatocytes are conducted.

• 日本トキシコロジー学会の論文
• 2000-10-25

著者

• WATANABE Takao

  Department of Environmental Health, Miyagi University of Education

• Tanaka Masahiro

  Department of Fixed Prosthodontics and Occlusion, Osaka Dental University

• Akashi Takumi

  Department Of Clinical Pathology Graduate School Of Medicine Tokyo Medical And Dental University

• Tanaka Masahiro

  Graduate School Of Dentistry (department Of Fixed Prosthodontics And Occlusion) Osaka Dental Univers

• Tanaka M

  Osaka Dental Univ. Osaka Jpn

• Tanaka Masahiro

  Dept. Of Toxicology Fuji Research Laboratoris Kowa Co. Ltd.

• Tanaka Masahiro

  Department Of Applied Chemistry

• Tanaka Masahiro

  Department Of Physics Tohoku University

• Akiba T

  Kowa Co. Ltd. Shizuoka Jpn

• Akiba Takashi

  Department Of Blood Purification Tokyo Women's Medical University

• Akiba Takashi

  Kidney Center Tokyo Medical And Dental University

• Watanabe Toshi

  Departments Of Veterinary Biochemistry College Of Bioresource Sciences Nihon University

• Akiba Tomohide

  Dept. Of Toxicology Fuji Research Laboratoris Kowa Co. Ltd.

• Akiba Takashi

  The Second Department Of Internal Medicine Tokyo Medical And Dental University School Of Medicine

• Tatsuta Mitsuhiro

  Department Of Fixed Prosthodontics And Occlusion Osaka Dental University

• 渡辺 稔之

  Medicinal Safety Research Laboratories Sankyo Co. Ltd.

• Tanaka M

  Graduate School Of Dentistry (department Of Fixed Prosthodontics And Occlusion) Osaka Dental Univers

• Akizawa Tadao

  Center Of Blood Purification Therapy Wakayama Medical School

• Takeshita Akira

  From Reseach Institute Of Angiocardiology And Cardiovascular Clinic Faculty Of Medicine Kyushu Unive

• Tatsuta M

  Department Of Fixed Prosthodontics And Occlusion Osaka Dental University

• Asai Tomoki

  Department Of Homeostasis Medicine And Nephrology Tokyo Medical And Dental University Graduate Schoo

• YAMAGUCHI Norikazu

  Dept. of Toxicology, Fuji Research Laboratoris, Kowa Co., Ltd.

• YAMAGUCHI Norikazu

  Department of Toxicology, Fuji Research Laboratories, Kowa Co., Ltd.

• AKIBA Tomohide

  Departments of Toxicology, Fuji Research Laboratories, Kowa Co., Ltd.

• TAKIMOTO Masayoshi

  Department of Toxicology, Fuji Research Laboratories, Kowa Co., Ltd.

• Yamaguchi Norikazu

  Dept. Of Toxicology Fuji Research Laboratoris Kowa Co. Ltd.

• Yamaguchi Norikazu

  Departmen T Of Pharmacology Kyoritsu College Of Pharmacy

• Watanabe Takao

  Department Of Applied Biology Kyoto Institute Of Technology

• Watanabe Takao

  Departmant Of Mathematics Faculty Of Science Osaka University

• Tanaka Masahiro

  Department Fixed Prosthodontics And Occlusion Osaka Dental University

• TANAKA Masahiro

  Department of Physics, Tohoku University

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