Williams E D
Department of Pathology, University of Wales College of Medicine, Cardiff, UK.
Toxicol Lett. 1992 Dec;64-65 Spec No:375-9. doi: 10.1016/0378-4274(92)90210-b.
The classic experimental model of thyroid neoplasia using radiation as a mutagen followed by long-term goitrogen treatment gives rise to multiple tumours in rats. Radiation alone, with suppression of TSH produces no tumours, TSH-induced growth alone causes a low level of tumorigenesis. Cell proliferation in this model is therefore critical. Epimutation as well as mutation is important. Rodent and human thyroid tumours show a clear stepwise progression, associated with both morphological and oncogene changes. In experimental animals the finding that monoclonal adenomas and carcinomas induced in the presence of long-term high TSH retain TSH dependency suggests that the step in the tumour progression requiring the development of TSH independent growth is bypassed, explaining the frequency of tumour development in this model. Normal thyroid follicular cell growth is limited, and a genotoxic effect before the growth plateau is more effective in carcinogenesis than a genotoxic effect after a period of growth. These observations will be interpreted in relation to the importance of thyroid tumours in regulatory toxicology and the pathobiology of thyroid tumours in man.
使用辐射作为诱变剂，随后进行长期致甲状腺肿物质治疗的经典甲状腺肿瘤实验模型会在大鼠体内引发多个肿瘤。单独使用辐射并抑制促甲状腺激素（TSH）不会产生肿瘤，单独的TSH诱导生长只会导致低水平的肿瘤发生。因此，该模型中的细胞增殖至关重要。表观突变以及突变都很重要。啮齿动物和人类甲状腺肿瘤呈现出明显的逐步进展，与形态学和癌基因变化相关。在实验动物中，发现在长期高TSH存在下诱导的单克隆腺瘤和癌保留了对TSH的依赖性，这表明肿瘤进展中需要发展出不依赖TSH生长的步骤被绕过了，这解释了该模型中肿瘤发生的频率。正常甲状腺滤泡细胞的生长是有限的，在生长平台期之前的遗传毒性作用在致癌过程中比在一段生长时期后的遗传毒性作用更有效。这些观察结果将结合甲状腺肿瘤在监管毒理学中的重要性以及人类甲状腺肿瘤的病理生物学进行解读。
