多种诱发小鼠舌癌模型方法的比较

Comparison of mouse model methods for tongue carcinoma

目的:建立小鼠舌癌模型,筛选诱癌率高及模拟人类发病的舌癌模型.方法:以Babl/c小鼠为实验对象,通过单独和联合应用4-硝基喹啉-1-氧化物(4NQO)和槟榔碱(Arecoline)来诱发舌癌,以涂布法采用质量浓度5mg/mL 4NQO;自然饮水法采用质量浓度20、50、100μg/mL 4NQO,采用质量浓度300μg/mL Arecoline及联合质量浓度100μg/mL 4NQO和质量浓度300μg/mL Arecoline.各组诱癌剂饮用至16或14周时,改为饮用灭菌自来水观察至第40周,于诱癌的不同节点选取状态不佳,体质量下降超过20%的小鼠处死,取其舌头、食管、胃、肝、脾脏组织标本,通过肉眼和组织学观察肿瘤发生发展情况.结果:自然饮水法质量浓度50μg/mL 4NQO组70.0%(7/10)为轻度不典型增生,40.0%(4/10)为中度不典型增生,20.0%(2/10)为重度不典型增生,10.0%(1/10)为原位癌;联合应用质量浓度为100μg/mL 4NQO和质量浓度为300μg/mL Arecoline组10.0%(1/10)为轻度不典型增生,20.0%(2/10)为中度不典型增生,40.0%(4/10)为重度不典型增生,20.0%(2/10)为原位癌,50.0%(5/10)为浸润癌,30.0%(3/10)淋巴结转移,20.0%(2/10)食管不典型增生.结论:质量浓度50μg/mL的4NQO饮用16周继续观察至40周是舌癌癌前病变动物模型建立的理想时间;质量浓度为100μg/mL的4NQO饮用14周后改饮用自来水至40周癌变发展缓慢、典型,发病率高,组织病理学特征与人相似.联合运用低剂量Arecoline和4NQO是诱癌率最高的建模方法,且可观察到颈部淋巴结转移及食管病变,但癌变进展快,不宜作为模拟人舌癌发病的模型.

Aim: To establish the tongue cancer model of mouse,screening models of high carcinogenesis rate or mimic human oral cancer. Methods: Babl/c mice were choosen as experimental subjects. Respectively and co-treated in different concentrations of chemical carcinogen 4-nitroqulnoline1-Oxide( 4 NQO)( Sigma Chemical C0.) and Arecoline in drinking water and painting was administered to mice. For all the experimental groups,oral lesions were induced by 4-NQO treatment for 16 or 14 weeks and then observed for additional weeks( 40 weeks of total observation). During the progress ofcarcinogenesis,mice were culled from the experiment group and then sacrificed if we observed a sudden weight loss of more than 20%. The tongue,esophagus,lymph nodes,gastrointestinal tract,liver,spleen,and kidney were carried out,observe the tumor progression by macroscopic and histopathological inspection. Results: The experimental group received 4-NQO( 50 μg/mL) showed Hyperkeratosis 60. 0%( 6/10),Mi DP 70. 0%( 7/10),Mo DP 40. 0%( 4/1 0),SDP 20. 0%( 2/10),ISC 10. 0%( 1/10); The group received both 4-NQO( 100 μg/mL) and arecoline( 300 μg/mL) showed Hyperkeratosis 90. 0%( 9/10),Mi DP 10. 0%( 1/10),Mo DP 20. 0%( 2/10),SDP 40. 0%( 4/10),ISC 20. 0%( 2/10),ICC 50. 0%( 5/10), Cervical lymph nody metastasis 30. 0%( 3/10), Esophagus atypical hyperplasia20%( 2/10). Conclusion: 16 weeks application of 50 μg/mL 4 NQ0 and additional then observed for an additional 24 weeks( 40 weeks of total observation). is the best period to preneoplastic induction. The group received 4-NQO( 100 μg/mL) model mimics human oral tumor formation. Cotreating with arecoline and 4-nitroquinoline 1-oxide can establish the highest canceration rate modeling method; but the mutagenesis and carcinogenes without apparente transformation process from precancerous lesions to invasive cancinoma were not suitable as a model that resembles human oral tumor formation.