4NQO饮水法诱发小鼠舌癌动物模型建立的研究

Mouse Tongue Epithelial Carcinoma Model of Induced by 4-nitroquinolinel-oxide in Drinking Water

目的：建立与人口腔癌发生相似的口腔癌动物模型。方法：0．001％四硝基喹啉-1-氧化物（4-nitroquinoline 1-oxide。4NQO）饮水喂养Balb／c小鼠16～28周，肉眼及组织学观察癌变全过程。结果：随4NQO作用时间和观察时间的延长，小鼠舌背后部黏膜相继出现白色斑块、红白相间斑块、乳头状新生物等改变。16周后50．0％小鼠舌背黏膜表现为轻度异常增生，45．0％为中度异常增生，5．0％为重度异常增生；20周后5．0％为轻度异常增生，60．0％为中度异常增生，30．0％为重度异常增生，5．0％为原位癌；24周后50．0％为中度异常增生，40．0％为重度异常增生，10．0％为原位癌；28周后30．0％为中度异常增生，50．0％为重度异常增生，10．0％为原位癌，10．0％为早期浸润性癌。用药16、20、24、28周停药观察至48周时，舌癌的发生率分别为0、14．3％、18．2％、28％，未见远处转移。结论：4NQO饮水诱发小鼠舌癌生长缓慢、潜伏期长，致癌过程和组织病理学特征与人相似，方法简便，靶器官代表性强；0．001％浓度4NQO饮用16～20周是舌癌前病变动物模型建立的理想时间，要在一定时间内建立发癌率更高的舌癌动物模型，用药的浓度需要加大。

Objective： To establish a mouse model for oral carcinogenesis which reveals histological and immunological characteristics similar to the human counterpart. Methods： 0. 001% 4NQO in drinking water was administered orally to Balb/c mouse for 16- 28 weeks. Then the mice were killed and their tongues were removed for histological assessment. Results： Gross changes included white changes, leukoplakia and erythroplakia appearances and verrucous hyperplasia on the posterior mucosa of the tongue dorsum of experimental group mice during carcinogenesis. The severity of lesions corresponded to the duration of treatment and length of observation. Their corresponding histopathological results ranged from hyperplasia, mild dysplasia（MiDP） , moderate dysplasia（MoDP） , severe dysplasia（SDP）, in situ carcinoma（ISC） to early invasive carcinoma（EIC）. The tongues of mice treated with 4NQO for 16 weeks showed MiDP （50.0%） , MoDP（45.0% ） and SDP （5.0%） ; the tongues of mice treated with 4NQO for 20 weeks showed MiDP （5.0%） , MoDP（60.0% ） , SDP （30.0%） , ISC（5.0% ） ; the tongues of mice treated with 4NQO for 24 weeks showed MoDP（50.0% ） , SDP（40.0% ） , ISC（ 10.0% ） ; and the tongues of mice treated with 4NQO for 28 weeks showed MoDP （30.0%） , SDP（ 50.0% ） , ISC （ 10.0% ） , EIC（ 10.0% ）. The incidence of tongue cancer in mice treated with 4NQO for 16 weeks, 20 weeks, 24 weeks, 28 weeks and then observed for 48 weeks was 0, 14.3% , 18.2% and 28% , respectively. No metastases were found. Conclusion： 4NQO can reliably induce mouse tongue preneoplastic lesions, carcinoma of the mouse tongue mucosa. The process of carcinogenesis and the biological behavior parallel to those of human oral carcinoma. The target organ is typical, and the method is handy. But the rate of tongue epithelial carcinoma is not high. 16 -20 weeks application of 0. 001% 4NQO is the best period to preneoplastic induction. Provided higher rate, of tongue epithelial carcinoma in the prescriptive time with higher rate, the concentration of 4NQO should be increased.