p53^＋/-基因敲除小鼠尿烷致癌性初步验证试验

Preliminary Carcinogenicity Validation Study of p53^(+/-) Knockout Mice Using Urethane

目的:观察自主建立的p53^(+/-)敲除小鼠(命名为B6-Trp53tm1/NIFDC)模型,在给予尿烷后的体重、脏器重量、血液学及血生化指标变化,为该模型将来用于临床前药物短期致癌性试验的替代试验提供背景数据。方法:共设计3个组:阴性对照组(野生型小鼠,给予生理盐水)、尿烷组1(B6-Trp53tm1/NIFDC小鼠,给予1000 mg·kg^(-1)尿烷)、尿烷组2(野生型小鼠,给予1000 mg·kg^(-1)尿烷),各组动物数量均为20只,雌雄各半。试验期间及试验结束测定各组动物的体重、脏器重量和相对脏器重量、血液学及血生化指标,并进行统计分析。结果与结论:与阴性对照组相比,尿烷给药第2、3、11及21周尿烷组1和尿烷组2动物的体重显著下降;尿烷组1动物肺脏和脾脏绝对重量显著升高;尿烷组1和尿烷组2动物肺脏相对重量显著升高;尿烷组1动物NEU、RDW%、CHDW%以及尿烷组2动物LYM%、BASO%显著升高;尿烷组1及尿烷组2动物的血生化指标无明显改变。

Objective： To observe the changes of body weight, organ weight, hematological and blood biochemical parameters of p53^（＋/-）knockout mice named as B6-Trp53 tm1/NIFDC, after administration of Urethane and to provide background data for using the p53^（＋/-）knockout model as an alternative model for short-term carcinogenicity study in the field of preclinical safety evaluation of drugs. Methods： A total of three different groups were used, including negative control group（wild type C57 BL/6 mice administrated with saline solution）, Urethane group 1（B6-Trp53 tm1/NIFDC mice administrated with 1000 mg·kg^（-1） Urethane） and Urethane group 2（wild type C57 BL/6 mice administrated with 1000 mg·kg^（-1） Urethane）. There were 20 mice in each group with 10 male mice and 10 female mice. The body weight, absolute organ weight, relative organ weight, hematological and blood biochemical parameters were measured during and after the test. Statistical analysis was carried out. Results and Conclusion： Compared with negative control group, the body weight of animals in Urethane group 1 and group 2 after 2, 3, 11 and 21 weeks in administration of Urethane decreased greatly. Both the absolute weight of the animals＇ lung and spleen in Urethane group 1 and the relative weight of the animals＇ lung in Urethane group 1 and Urethane group 2 significantly increased. The levels of NEU, RDW% and CHDW of Urethane group1 and LYM% and BASO% of Urethane group 2 significantly increased. There was no significant change of the blood biochemical parameters in Urethane group 1 and Urethane group 2.