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Carcinogen-induced Thyroid Proliferative Lesions in Wistar Hannover GALAS Rats with Thyroid Dysplasia
Authors:Abe Masayoshi  Hayashi Seigo  Usuda Koji  Hagio Soichiro  Furukawa Satoshi  Nakae Dai
Institution:1. Toxicology and Environmental Science Department, Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama-gun, Saitama 349-0294, Japan;2. Department of Pharmaceutical Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku, Tokyo 169-0073, Japan;3. Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya, Tokyo 156-8502, Japan
Abstract:Incidences and morphological features of thyroid proliferative lesions induced by carcinogens in Wistar Hannover GALAS rats (GALAS rats) showing normal growth with or without thyroid dysplasia were examined. All thyroid tissue samples were obtained from our recently conducted study using male GALAS rats treated with 5 carcinogens according to the medium-term multiorgan carcinogenicity bioassay protocol (called DMBDD treatment). In the DMBDD-treated rats, thyroid dysplasia was found in 9 out of 114 rats. Follicular cell adenomas were found in 5 out of 9 rats with thyroid dysplasia and in 7 out of 105 rats without thyroid dysplasia. The incidence of adenoma was significantly increased in rats with thyroid dysplasia (55.6%) compared with that in rats without thyroid dysplasia (6.7%). Adenomas in rats with thyroid dysplasia were observed as single or multiple nodules, well demarcated and composed of variously sized vacuolated cells or unvacuolated cells. These histopathological features and staining profiles of luminal colloid for PAS and thyroglobulin, together with PCNA-positive cells, were fundamentally similar to those of rats without thyroid dysplasia. On the other hand, the luminal colloid in adenomas of rats with thyroid dysplasia had a tendency to be poorly stained for T(4) compared with that of rats without thyroid dysplasia. From these findings, it appears that dysplastic thyroids of rats showing normal growth are more sensitive to carcinogens than normal thyroids. In addition, the morphological features of carcinogen-induced thyroid proliferative lesions in GALAS rats with thyroid dysplasia were fundamentally similar to those of rats without thyroid dysplasia, except for the vacuoles and T(4) staining profile.
Keywords:multiorgan carcinogenesis model  thyroid dysplasia  thyroid proliferative lesion  Wistar Hannover GALAS rats
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