两种浓度4NQO饮水法诱发小鼠舌癌及癌前病变动物模型的比较

Two Concentrations of 4NQO Water Law Induced Animal Model of Tongue Cancer and Precancerous Lesions.

目的：快速、准确的建立与人舌癌及癌前病变发生相似的动物模型。方法：0．001％和0．002％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，小鼠舌黏膜相继出现白色斑块、红白相间斑块、乳头状新生物、溃疡等改变。饮用0．001％4NQO 16周后的小鼠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124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；饮用0．002％4NQO16、20、24、28周停药观察至40周的小鼠，舌癌的发生率分别为10％、25％、37．5％、45．5％，未见远处转移。结论：4NQO饮水法诱发小鼠舌癌及癌前病变生长缓慢、潜伏期长，致癌过程和组织病理学特征与人相似，方法简便；0．001％是诱发小鼠舌癌前病变的理想浓度，0．002％是诱发小鼠舌癌的理想浓度。

Objective：To establish a mouse model for tongue epithelial carcinoma and precancerous lesions which reveals histological and immunological characteristics similar to the human counterpart. Methods： 0. 001% 和0. 002% 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 , erythroplakia appearances, verrucous hyperplasia on the mucosa of the tongue of experimental group mice during carcinogenesis. The severity of lesions corresponded to the duration of treatment and length of observation. Their corresponding histopatho- logical 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 0. 001%4NQO for 16 weeks showed MiDP （50.0%）, MoDP（45.0% ） and SDP （5.0%） ; the tongues of mice treated with 0. 001% 4NQO for 20 weeks showed MiDP （5.0%）, MoDP（60.0% ）, SDP（ 30.0% ） and ISC （5.0%） ; the tongues of mice treated with 4NQO for 24 weeks showed MoDP（50.0% ）, SDP（40.0% ） and ISC（ 10.0% ）. The incidence of tongue cancer in mice treated with 0. 002%4NQO for 16 weeks, 20 weeks, 24 weeks, 28 weeks and then observed for 40 weeks was 10%, 25%, 37. 5% and 45.5%, 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. 0.001% is the best concentration to induce the mouse model of precancerous lesions and 0.002% is the best concentration to induce the mouse model of tongue epithelial carcinoma.