Molecular pathology of thyroid tumorigenesis

1. 用二异丙醇亚硝胺（DIPN）诱导大鼠甲状腺肿瘤建立了3个细胞系。这些细胞以单层方式生长，在免疫染色方面未能表现出甲状腺球蛋白合成能力。这些肿瘤可移植到裸鼠身上，分化和甲状腺球蛋白合成较低。对DIPN诱导的大鼠甲状腺肿瘤进行组织病理学和免疫组化研究，探讨甲状腺癌的组织发生机制。在目前的实验条件下，获得的数据支持肿瘤发生的多阶段假说，而不是肿瘤发展的从头假说。溴脱氧尿苷（Bromodeoxyuridine, BrdU）标记法在恶性病变中生长活性最高。采用DIPN诱导大鼠甲状腺肿瘤，探讨雄激素在甲状腺癌变中的可能作用。结果表明，雄激素对肿瘤的发展起刺激作用。放射自显影研究和受体结合试验的结果支持了雄激素通过与甲状腺细胞的核受体结合而刺激肿瘤生长的观点。免疫组化对DIPN诱导大鼠甲状腺病变中铜锌锰超氧化物歧化酶（SOD）定位的研究结果提示，SOD活性的改变可能与甲状腺肿瘤发生有关，并且存在SOD表达的调控机制。

1. Three cell lines have been established from diisopropanolnitrosamine (DIPN) induced rat thyroid tumors. These cells grow in monolayer fashion and failed to demonstrate the capability of thyroglobulin synthesis in terms of its immunostaining. These tumors showed transplantable to nude mice with loered differentiation and thyroglobulin synthesis.2. Histopathological and immunohistochemical studies were conducted on rat thyroid tumors induced by DIPN to elucidate the histogenesis of thyroid carcinoma. The data obtained supported the multistage hypothesis of tumorigenesis rater than the de novo hypothesis of tumor development under the present experimental conditions. Bromodeoxyuridine (BrdU) -labelling method proved the highest growth activity in the malignant lesions.3. Employing DIPN induced rat thyroid tumors, the possible role of androgens in thyroid carcinogenesis was examined. The results suggested that androgens acted as a stimulatory factor to the development of tumors. The results of an autoradiographic study and a receptor binding assay supported the idea that the tumor growth is stimulated by androgens through binding with the nuclear receptor of the thyrocytes.4. The findings of the immunohistochemical study on the localization of copper-zinc and manganese superoxide dismutases (SOD) in DIPN induced rat thyroid lesions suggested a possible correlation between alterations of SOD activities and thyroid tumorigenesis, and the existence of regulatory mechanism for SOD expression.