Okamura Miwa, Yasuhara Kazuo, Koujitani Takatoshi, Nasu Masahiro, Hirose Masao, Mitsumori Kunitoshi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchuu-city, Tokyo, 183-8509, Japan.
Toxicology. 2003 Jun 30;188(2-3):275-83. doi: 10.1016/s0300-483x(03)00093-3.
To clarify the threshold dose of thyroid tumor-promoting effects of xylazine hydrochloride (XZ), male F344 rats received pulverized basal diet containing 0, 250, 500, or 1000 ppm XZ for 26 weeks with or without initiation of 2400 mg/kg N-bis(2-hydroxypropyl)nitrosamine (DHPN). Thyroid weights significantly increased in the groups with or without DHPN initiation that were given 500 ppm XZ or more. The serum thyroxine (T4) and triiodothyronine (T3) levels decreased significantly in the XZ 250 and XZ 1000 ppm groups, respectively, although there were no remarkable changes in the serum thyroid-stimulating hormone (TSH) levels. Histopathologically, follicular cell hyperplasias and adenomas were induced in the DHPN-alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN groups treated with 500 ppm XZ or more were significantly higher than those in the DHPN alone group. These results suggest that the threshold dose of rat thyroid tumor-promoting effects of XZ is between 250 and 500 ppm under the present experimental condition.
为明确盐酸赛拉嗪（XZ）促进甲状腺肿瘤发生的阈剂量，雄性F344大鼠分别摄入含0、250、500或1000 ppm XZ的粉碎基础饲料26周，部分大鼠同时或不同时给予2400 mg/kg N-双（2-羟丙基）亚硝胺（DHPN）进行启动处理。在给予500 ppm及以上XZ的组中，无论是否进行DHPN启动处理，甲状腺重量均显著增加。XZ 250 ppm组和XZ 1000 ppm组的血清甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平分别显著降低，而血清促甲状腺激素（TSH）水平无明显变化。组织病理学检查发现，单独给予DHPN组和DHPN + XZ组均出现滤泡细胞增生和腺瘤，给予500 ppm及以上XZ处理的DHPN组中这些病变的发生率和多发性显著高于单独给予DHPN组。这些结果表明，在本实验条件下，XZ促进大鼠甲状腺肿瘤发生的阈剂量在250至500 ppm之间。
