云锡矿粉诱发F344大鼠肺癌的病理改变

目的建立云锡矿粉（无氡）诱发F344大鼠肺癌的动物模型，探讨其肺癌发生过程及不同阶段的病理变化。方法190只大鼠随机分为矿粉组（100只）、呋喃甲醛组、生理盐水组及正常对照组（各30只）。除正常对照组外，其他3组分别以质量分数为6％的矿粉悬液、体积分数为2％的呋喃甲醛及生理盐水每次0．2ml经气管灌注，每周1次，从灌注1周后定期分批处死大鼠，最后处死的1只大鼠染尘100周。光学显微镜及电子显微镜观察矿粉作用下肺组织的形态改变，免疫组化检测高分子和低分子角蛋白确定诱发肺癌的组织类型，Pollak染色观察肺纤维化的进展。结果矿粉组大鼠最早期出现肺部炎症，随着炎症消退见肺间质纤维增生，肺泡及支气管上皮单纯性增生、乳头状增生及鳞状化生，继而出现肺泡非典型腺瘤样增生、鳞状上皮非典型增生，最终出现肺癌。共发生肺癌14例，其中腺癌9例、鳞癌2例、复合癌3例，其他3组均未发生肺癌，矿粉组癌变率与其他3组比较，差异有统计学意义（P〈0．01）。鳞状化生及鳞癌也可发生于肺泡并表达高分子角蛋白。矿粉组肺纤维化31例，纤维化程度随矿粉沉着增多而呈进行性加重。结论无氡云锡矿粉具有诱癌性，F344大鼠矿粉诱发性肺腺癌及鳞癌都可发生于肺泡，Ⅱ型肺泡上皮是否是肺腺癌及外周型肺鳞癌的起源细胞值得深入研究。

Pathological study of lung cancer induced by Yunnan tin mine dusts in F344 rats

OBJECTIVE: To set up animal models of the lung cancer induced by Yunnan tin mineral dusts (no radon) in F344 rats and to explore the process of carcinogenesis and pathologic alterations in various stages of malignant transformation in the animal models. METHODS: One hundred and ninety F344 rats were randomly divided into Yunnan tin mineral dust group (100 rats), furfural physiological saline group (30 rats), physiological saline group (30 rats) and normal control group (30 rats). The intratracheal instillation with mass fraction of 6% suspension liquid mixture Yunnan tin mineral dusts, volume fraction of 2% furfural physiological saline and physiological saline 0.2 ml was performed in the rates once per week respectively except normal control group. Then the rats were sacrificed in batch periodically after one week. The last rat was exposed to the tin mine dusts for 100 weeks. The morphological process and tumor formation were dynamically observed under LM and TEM. Immunohistochemistry detection of cytokeratin of High MW and low MW was used for tumor classification. Pollak stein was used to evaluate the development of fibrosis of lung in the rats. RESULTS: Bronchoalveolar inflammation occurred in the early stage after the intratracheal instillation of Yunnan tin mineral dust was performed in F344 rates. Along with reduction of inflammation, collagen fibrils increased at alveolar interstices. Simple hyperplasia, papillary hyperplasia and metaplasia of the epithelial cells in alveolar and bronchi were observed, followed by atypical adenomatous hyperplasia and squamous dysplasia. Lung cancer was induced in the end. Among the 14 cases of lung cancer, 9 cases were adenocarcinoma, 2 squamous cell carcinoma and 3 mixed carcinoma. No lung cancer occurred in other three control groups. There was a significant difference in the malignancy rate between the experimental group and the three control groups (P < 0.01). The squamous metaplasia and squamous carcinoma were found in alveoli that expressed cytokeratin of High MW. Lung fibrosis was found in 31 cases of in the tin mineral dust group. The greater the mineral dust deposit was, the more serious the alveolar fibrosis was. CONCLUSION: Yunnan tin mineral dusts without radon induce lung cancer in rates. The adenocarcinoma and squamous carcinomas induced in F344 rat lung can occur in the alveoli. The further study on whether type II alveolar epithelial cells are the origin cells of adenocarcinoma and some peripheral squamous lung carcinomas is worthwhile.