二甲基苯蒽/佛波酯两步化学法诱导小鼠皮肤癌的模型优化

Optimization of the establishment protocol of a mouse model of MBA/TPA-induced skin cancer

目的对两步化学诱导法建立BALB/c小鼠皮肤癌模型进行方法优化。方法将BALB/c小鼠背部剃毛暴露出约2 cm×2 cm的皮肤,小鼠随机分为空白对照组和4个模型组,4个模型组第1周分别涂1、2、4、7次100μg/100μL DMBA/丙酮液,后续均1周涂两次4μg/100μL TPA/丙酮液,记录小鼠体重、成瘤时间、成瘤数量,并在12周后处死小鼠取肿瘤组织及瘤旁组织做HE染色分析。结果 1周涂1次DMBA成瘤周期长;1周两次成瘤周期短,质量高;1周4次会损伤皮肤但不影响肿瘤的形成;1周7次对皮肤伤害较大并导致小鼠死亡。结论采用第1周涂两次DMBA启动,后续用TPA连续诱导建立BALB/c小鼠皮肤癌模型操作简便,成瘤期短,癌变率高,与人类皮肤癌发生发展相似,可用于建立研究皮肤癌较为理想的实验动物模型。

Objective To induce skin cancer in BALB/c mice using DMBA as initiator and TPA as tumor promoter. Through optimizing the doses and frequencies of DMBA administration to establish a stable skin cancer model with less time and causing less skin damage. Methods Shaving the back of mice to expose a piece of skin around 2 cm × 2 cm.The mice were divided into a blank control group and four treatment groups randomly. These four groups were given 1,2,4,7 times 100 μg /100 μL DMBA / acetone,respectively,in the first week,and twice 4 μg /100 μL TPA / acetone per week in the next 11 weeks. The body weight changes,time of tumor formation and number of tumors formed were recorded during the experiment. The mice were sacrificed at 12 th week and samples of tumor tissue and adjacent normal skin tissue were taken for pathological examination using HE staining. Results Tumors were observed at the 7th week in the group with once DMBA administration in the first week and at the 4th week in the group with twice DMBA administration in the first week. Skin cancers were formed also in the group with 4-time DMBA administration in the first week,however,with significantly more severe skin damages. The mice receiving DMBA everyday in the first week died at the 3th week. Conclusions The best induction protocol for skin cancer in BALB / c mice should be twice DMBA in the first week followed by twice TPAin the next few weeks. This protocol has the advantages of easy operation,short modeling time,high cancer formation rate,and presents a similar process of human skin carcinogenesis,thus,it can be used as a useful animal model for skin cancer research.