COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 10)TESTICULAR TOXICITY OF ADRIAMYCIN OBSERVED 2 AND 4 WEEKS AFTER A SINGLE INTRAVENOUS ADMINISTRATION
スポンサーリンク
概要
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The present study was performed to clarify whether toxic effects of the antitumor drug, adriamycin (ADR) on the male genital organ can be adequately detected 2 and 4 weeks after a single intravenous administration in the rat. ADR was intravenously administered once to 10 Crj:CD (SD) male rats/group aged 6 weeks (4-week group) and 8 weeks (2-week group) at doses of 0, 2 and 6 mg/kg. The rats were sacrificed at the age of 10 weeks. For comparison 10 rats/group were killed 2 weeks after a single intravenous administration at the age of 4 weeks (immature group). Saline was administered to control rat. Histopathological examination and a quantitative morphometry were carried out after measurement of testes weights at necropsy. In rats of the 4-week and 2-week groups, mean absolute testicular weight in all groups was significantly decreased. However, changes in mean relative weight were not evident in the 2-week group. Disappearance of seminiferous epithelial cells was observed histopathologically in rats dosed with 2 and 6 mg/kg in the 2-week group. The change was more severe in the 4-week group, when reduction of spermatogenesis and giant cells were also observed at 6 mg/kg. The quantitative morphometry in the 2-week group showed decreases in the numbers of spermatogonia and spermatocytes in stages X and XII at 2 mg/kg, and in the numbers of spermatogonia in all stages and spermatocytes in all stages except stage V at 6 mg/kg. Moreover, the numbers of spermatogonia and spermatocytes in all stages and spermatids in stages II-III and V were decreased with dose related manner in the 4-week group. In contrast, no obvious change in testes weights was apparent in the immature group. However, the numbers of spermatogonia and spermatocytes in all stages were decreased at 6 mg/kg. In conclusion, testicular toxicity of ADR could be detected 2 weeks after a single administration. Susceptibility of the testes of immature rats to ADR might be less than that of older animals.
- 日本トキシコロジー学会の論文
- 2000-10-25
著者
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KAWACHI Mamoru
Department of Toxicology and Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehring
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Kawachi Mamoru
日本ベーリンガーインゲルハイム川西医薬研究所
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Kawachi Mamoru
Dept. Of Toxicol. & Safety Assess. Kawanishi Pharma Res. Institute Nippon Boehringer Ingelheim C
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Kawachi Mamoru
Department Of Toxicology And Safety Assessment Kawanishi Pharma Research Institute Nippon Boehringer
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TSUNENARI Ichiro
Department of Toxicology & Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer
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MATSUMARU Takehisa
Department of Toxicology & Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer
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KATSUKI Shoji
Department of Toxicology & Safety Assessment, Kawanishi Pharma Research Institute, Nippon Boehringer
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Katsuki Shoji
Dept. Of Toxicol. & Safety Assess. Kawanishi Pharma Res. Institute Nippon Boehringer Ingelheim C
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Tsunenari Ichiro
Dept. Of Toxicol. & Safety Assess. Kawanishi Pharma Res. Institute Nippon Boehringer Ingelheim C
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Matsumaru Takehisa
Division Of Molecular Pharmacology And Pharmacogenomics Department Of Genome Sciences Kobe Universit
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Matsumaru Takehisa
Dept. Of Toxicol. & Safety Assess. Kawanishi Pharma Res. Institute Nippon Boehringer Ingelheim C
関連論文
- KEY PARAMETERS OF SPERM MOTION IN RELATION TO MALE FERTILITY IN RATS GIVEN α-CHLOROHYDRIN OR NITROBENZENE
- P-81 Collaborative work to evaluate toxicity on male reproductive organs in rats. : Taesticular toxicity of adriamycin observed 2 and 4 weeks after a single intravenous administraion(Proceedings of the 27th Annual Meeting)
- COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 10)TESTICULAR TOXICITY OF ADRIAMYCIN OBSERVED 2 AND 4 WEEKS AFTER A SINGLE INTRAVENOUS ADMINISTRATION
- Comparison of Toxicity and Toxicokinetics/Pharmacokinetics of an α_-Adrenoceptor Agonist in Rats and Rhesus Monkeys
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