丝裂霉素C诱导的Wistar大鼠器官毒性：一项特别关注肾脏的研究
Mitomycin C-induced organ toxicity in Wistar rats: a study with special focus on the kidney.
作者信息
Verweij J, Kerpel-Fronius S, Stuurman M, van Triet A J, van Hattum L, de Vries J, Pinedo H M
机构信息
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
出版信息
J Cancer Res Clin Oncol. 1988;114(2):137-41. doi: 10.1007/BF00417827.
Two studies were performed to investigate acute and chronic organ toxicity after Mitomycin C (MMC) administration in Wistar rats. Six rats received 2.5 mg/kg MMC i.p. once and were followed for 5 consecutive days. The alanine aminopeptidase (AAP)/creatinine ratio increased significantly, compared to a control group receiving saline. Four groups of rats were injected i.p. weekly for 5 weeks; 6 control rats with saline, 7 rats with 1.7 mg/kg of MMC, 7 rats with 10 mg/kg 5-fluorouracil (5-FU) and 7 rats with MMC as well as 5-FU. The latter two groups were included to study possible toxicity synergism between the two drugs. A significant decrease in AAP excretion in the MMC group, as well as a nonsignificant decrease in the MMC/5-FU group were the most remarkable observations. Light microscopy did not show renal changes, but did not show alveolar septal congestion after repeated MMC injections. It is concluded that MMC causes tubular damage in Wistar rats, with acute leakage of enzyme from the cells, followed by enzyme depletion during chronic treatment. Also MMC induces pulmonary changes in Wistar rats. To what extent these changes represent early stages of toxicity remains to be elucidated.
进行了两项研究，以调查丝裂霉素C（MMC）对Wistar大鼠给药后的急性和慢性器官毒性。六只大鼠腹腔注射2.5mg/kg MMC一次，并连续观察5天。与接受生理盐水的对照组相比，丙氨酸氨基肽酶（AAP）/肌酐比值显著升高。四组大鼠每周腹腔注射一次，共注射5周；6只对照组大鼠注射生理盐水，7只大鼠注射1.7mg/kg MMC，7只大鼠注射10mg/kg 5-氟尿嘧啶（5-FU），7只大鼠同时注射MMC和5-FU。纳入后两组以研究两种药物之间可能的毒性协同作用。最显著的观察结果是MMC组AAP排泄显著减少，以及MMC/5-FU组非显著减少。光学显微镜检查未显示肾脏变化，但多次注射MMC后未显示肺泡间隔充血。结论是MMC在Wistar大鼠中引起肾小管损伤，细胞内酶急性泄漏，随后在慢性治疗期间酶耗竭。此外，MMC在Wistar大鼠中诱导肺部变化。这些变化在多大程度上代表毒性的早期阶段仍有待阐明。
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