4-硝基喹啉-1-氧化物诱导C57BL/6小鼠舌黏膜癌变的研究

Study on lingual mucosa carcinogenesis of C57BL/6 mice induced by 4-nitroquinoline 1-oxide

目的用4-硝基喹啉-1-氧化物（4NQO）诱导C57BL/6小鼠舌黏膜癌变。方法将85只小鼠随机分为蒸馏水对照组（n=5）、1,2丙二醇对照组（n=5）、实验组（n=75）,分别给予蒸馏水、1,2丙二醇及4NQO溶液饮用。实验组小鼠再分为15笼,每2周处死一笼,对照组小鼠于28周处死。对小鼠进行称质量和大体观察及组织病理学检查。结果实验组死亡1只。实验组小鼠体质量在24周后体质量较对照组明显降低（P〈0.05）。实验动物的舌、口底、上颚、颊部共出现79处肉眼可见的病变,其中舌部病变70处（88.6%）。实验组动物在不同时间点黏膜病变不同,28周时均发生高分化鳞状细胞癌。对照组未见病变。结论舌癌动物模型被成功建立。实验12~16周及20~28周可作为研究舌黏膜癌变早期和中晚期阶段的时间点。

Objective This study aimed to induce carcinogenesis of lingual mucosa in C57BL/6 mice by feeding them 4-nitroquinoline 1-oxide（4NQO） solution. Methods A total of 85 C57BL/6 mice were randomly divided into distilled water control group（DD group, n=5）, 1,2-propylene glycol control group（PG group, n=5）, and experimental group（EP group, n=75）. The mice in the experimental group were medially fed in 15 cages. By contrast, the mice in DD, EP, and PG groups were watered with distilled water, 50 mg·L-1 4NQO solution, and 1,2-propylene glycol solution. The mice in EP group were executed every two weeks from week 0, and the mice in the control groups were sacrificed at the 28 th week. The mice were weighed. Mucosal lesions were measured by macroscopic observation and histopathologic detection. Results One mouse in EP group died of unknown reason. The weight of the mice in EP group presented weight loss compared with the mice in DD and PG groups after the 24 th week. Seventy-nine macroscopic lesions were observed in the lingual mucosa, oral floor, and upper palatal and buccal mucosa. A total of 70 macroscopic lesions（88.6%） were located in the lingual mucosa. Mucosal lesions changed from simple hyperplasia to squamous cell carcinomas. Well-differentiated squamous cell carcinomas were observed in all mice of EP group by pathological section at the 28 th week. No lesion was found in the mice of DD and PG groups. Conclusion The animal model of lingual squamous cell carcinomas was successfully established. The periods from 12 th to 16 th week and 20 th to 28 th week were the ideal times for the research on pathogenesis of early and medial-advanced stage during carcinogenesis of squamous cell carcinomas.