米非司酮多次用药对大鼠子代安全性的研究

对米非词酮多次用药后大鼠子代的生长发育、生殖毒性、遗传毒性以及形态变化等进行了研究。 SD大鼠雌雄合笼妊娠后 ,于妊娠第 7～ 9天 ,每天给米非司酮 4 mg/ kg(抗早孕剂量 ) ,以终止妊娠。两周后重复以上步骤 ,并终止第二次妊娠。然后每天给米非司酮 1 mg/ kg共 1 4天。再与雄鼠合笼 ,于确定妊娠当天开始 ,每天给米非司酮 0 .5mg/kg1 5天。至孕 2 0天 ,半数鼠解剖取材 ,余鼠产仔 ,观察各项指标。结果表明 ,米非司酮多次用药对大鼠胚胎的肝脏淋巴细胞染色体畸变率、微核率 ,以及幼鼠骨髓细胞姐妹染色单体互换率 (SCE) ,均未见明显的遗传学影响 ;出生的幼鼠生长发育良好 ,所测各项有关生殖毒性及形态变化指标与对照组无明显差异。本检测的结果显示 ,米非司酮不引起大鼠子代的遗传学改变。

Safety of progeny after repeated use of mifepriston in rats

Objective: To investigate the growth rate, the organ morphology and the reproductive and genetic toxicity in the progeny of rats after repeated doses of mifepristone. Methods: Female rats were cohabited with the males and on day 7～9 of gestation, the females were given mifepristone at a dose of 4 mg/kg·d for 3 days (the anti early pregnancy dose)to terminate the gestation. The procedure was repeated 2 weeks later and the second pregnancy was terminated as well. After that the rats were given mifepristone at 1 mg/kg·d for 14 days and were then cohabited with the males. On day 1 of pregnancy, mifepristone was again administered at a dose of 0.5 mg/kg·d for another 15 days. On day 20 of gestation, 50% of the rats were sacrificed for various examinations, the remaining animals were fed up to the time of delivery for the observation of other parameters. Results: The chromosome aberration and micronuclei rates of the fetal liver lymphocytes, and the sister chromatid exchange rate in the bone marrow cells of the young rats were not significantly different from those of the controls. The growth rate, the organ morphology and parameters related to reproductive toxicity in the young rats were also similar to those of the controls. Conclusion: The repeated use of mifepriston did not give rise to apparent geneticand reproductive toxicity. From the results of the present paper, the authors beli eve that the clinical use of mifepristone should be safe.