摘要
背景与目的:研究新型抗肿瘤化合物MC004对雄性大鼠的生殖毒性。材料与方法:健康成熟雄性Wistar大鼠48只,随机分为3个实验组和1个对照组,实验组分别隔日尾静脉注射给予0.25、0.50、0.75 mg/kg的MC004,共28 d。对照组给予相同体积的生理盐水。给药结束后24 h剖杀动物,用计算机辅助精子分析系统分析精子数量和活力,显微镜下观察精子形态。结果:与对照组相比,MC004 0.75 mg/kg组大鼠体重增长缓慢;各给药组大鼠睾丸、附睾的绝对重量及脏器系数均显著降低(P<0.01);各给药组大鼠的精子数量显著降低(P<0.01),0.50 mg/kg和0.75 mg/kg剂量组的精子运动速度降低明显(P<0.01);各实验组大鼠均出现大量畸形精子(P<0.01)。结论:MC004隔日按0.25 mg/kg剂量尾静脉注射,28 d后即对雄性大鼠生殖系统产生明显毒性。
BACKGROUND AND AIM： To study the effects on reproduction of male rats caused by the new antitumor compound, MC004. MATERIALS AND METHODS： 48 healthy and mature Wistar rats were randomly divided into 4 groups with 12 in each group. The rats of control group were given intravenous injections with normal saline and the exposure groups received MC004 at doses of 0.25,0.50 and 0.75 mg/kg. All rats were injected once in two days. All 48 rats were sacrificed after 28 days. Sperm motility was analyzed by a computer-assisted sperm analysis system and the sperm morphology was examined by microscope. RESULTS： The body weight was slowly increased and there was a significant difference between the dose of 0.75 mg/kg and the control group. Both the absolute weight and the organ weight to body weight ratios for testis and epididymis were significantly decreased（P 〈 0.01）. The epididymal cauda sperm number and the motility of the sperms were significantly decreased by MC004 treatment, while the rate of abnormal sperms was inereased（P 〈 0.01） . CONCLUSION： When the male rats were treated with intravenous MC004 once in two days for 28 days, there was significant reproductive toxicity at the dose of 0.25 mg/kg.
出处
《癌变．畸变．突变》
CAS
CSCD
2009年第3期218-221,共4页
Carcinogenesis,Teratogenesis & Mutagenesis
基金
重大新药创制科技重大专项(2008ZX09305-003)
北京市科委科技计划"创新药物研究开发"项目(D07080201330721)
北京市自然科学基金项目(7092079)
