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出 处:《中国药理学与毒理学杂志》2006年第4期318-322,共5页Chinese Journal of Pharmacology and Toxicology
摘 要:目的研究不同生长阶段ICR小鼠对己烯雌酚(DES)暴露的敏感性及DES暴露频率与肿瘤发生的关系,探索乌垃坦(Ure)对DES的肿瘤促进作用。方法新生及5周龄小鼠分对照、溶剂、DES、Ure及Ure+DES联合应用组。新生鼠在d 14,5周龄鼠在出生第5周末,均以500 m.gkg-1Ure ip;新生鼠分别在d 1,8和15 ip DES共3次;5周龄鼠从出生第6周起ip DES,每周1次,连续18次。至26周时剖检,观察肿瘤发生情况。结果新生鼠和5周龄鼠均有明显的肺肿瘤发生。新生鼠DES(2.0,4.0和8.0 m.gL-1)给药组,肺肿瘤发生率分别为16.7%,22.4%和43.1%;Ure+DES(2.0,4.0和8.0 m.gL-1)为70.4%,90.9%和70.8%。5周龄鼠DES 5,15及50 mg.kg-1时,肺肿瘤发生率分别为52.5%,32.1%和23.0%;Ure+DES(5,15和50 m.gL-1)为54.1%,58.5%和62.0%。结论外源DES对同一品系小鼠不同生长阶段的致肿瘤作用不同,新生鼠比成年鼠对DES和Ure联合作用有更高的肿瘤易感性,Ure对DES有一定的肿瘤促进作用。AIM To study the susceptibility to tumorigenetic effect of diethylstilbestrol (DES) in different periods of mouse life and the promotion of urethane (Ure). METHODS The neonatal and 5-week-old mice were exposed to DES and/or Ure . The new born mice were exposed to different dose of DES by ip on d 1,8 and 15, respectively while Ure was injected ip on d 14. Ure 500 mg·kg-1 was injected ip in 5-week-old mice, one week later and there after DES was injected ip once time every week for 18 weeks. When treated mice were 26 weeks old, they were sacrificed to examine the tumor. RESULTS Lung tumors were induced apparently both in neonatal and in 5-week-old mice. The incidence of lung tumor in neonatal mice was 16.7%, 22.4% and 43.1%, respectively in the DES(2.0, 4.0 and 8.0 mg·kg-1) group, whereas that in the Ure + DES (2.0,4.0 and 8.0 mg·kg-1 90.9% and 70.8%, -1 ) group was 70.4% , respectively. The rate of lung tumor in 5-week-old mice at DES 5, 15 and 50 mg·kg-1 was 52. 5%, 32. 1% and 23.0%, respectively, that in the Ure + DES (5, 15 and 50 mg·kg-1) was 54.1% , 58.5% and 62. 0%, respectively. CONCLUSION Carcinogenic activity is varied with developmental periods of ICR mice exposed to DES. The new born mice may have high susceptibility than adults when exposed to Ure + DES. Ure apparently has the promotion effect on the lung tumorigenesis of DES.
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