紫外线所致皮肤鳞状细胞癌小鼠模型的建立

Establishment of mouse model for cutaneous squamous cell carcinoma induced by ultraviolet

目的应用日光模拟器模拟日光照射SKH-1无毛小鼠，建立皮肤鳞状细胞癌（鳞癌）动物模型，探讨其生物学特性。方法将91只SKH-1无毛小鼠随机分成7个实验组（每组10只）和7个对照组（每组3只）。实验组每天给予红斑量日光紫外线照射，对照组不做任何处理；在第4、8、12、16、20、24、28周分别处死小鼠行病理检查。实验过程中观察小鼠一般状态和照射区域皮肤变化，分析各期小鼠皮损特点及组织学变化。结果10周后实验组部分小鼠陆续出现直径≥1mm的丘疹，紫外线照射20周开始实验组剩余小鼠中39．3％出现肿瘤（11／28），照射28周后成瘤率达100％（10／10），累计UVB剂量约为26．99J／cm^2，UVA剂量约为242．91J／cm^2。对照组未见肿瘤形成。照射各时期组病理显示，12周30％、16周33．3％、20周60％、24周87％、28周100％的小鼠具有鳞癌特征。结论紫外线照射可诱导SKH-1无毛小鼠皮肤组织增生，并随照射时间延长产生皮肤鳞癌。

Objective To establish a model for cutaneous squamous cell carcinoma by irradiation of SKH-1 hairless mice with solar-simulated ultraviolet （solar UV）, and to explore the biological characteristics of the model. Methods A total of 91 SKH-1 hairless mice were randomly divided into seven experimental groups （n = 10） and seven control groups （n = 3）. The mice in experimental groups were irradiated with minimal erythema dose of solar UV 4 times per week for various durations （4, 8, 12, 16, 20, 24, 28 weeks）, while the control mice received no irradiation. The general status and skin appearance of mice were observed during the treatment process. Mice were killed immediately after the last irradiation at different time points and pathological examination was carried out to observe the histological changes of skin lesions. Results Papules measuring equal to or more than 1 mm in diameter began to develop in some mice in experimental group 10 weeks after the first irradiation; tumors began to appear in 39.3% （11/28） of the remaining mice in experimental group on week 20, and in 100% （10/10） of the remaining mice on week 28. The cumulative dose approximated to 26.99 J/cm2 for UVB and 242.91 J/cm2 for UVA after 28-week irradiation. No tumor was observed in the control mice. Pathological examination revealed characteristic changes of squamous cell carcinoma in 30% of the mice on week 12, 33.3% on week 16, 60% on week 20, 87% on week 24, and 100% on week 28. Conclu- sions Ultraviolet could induce the hyperplasia of skin in SKH-1 hairless mice, and even cause the development of cutaneous squamons cell carcinoma after prolonged irradiation.