Yasuhara K, Koujitani T, Takegawa K, Nasu M, Onodera H, Takagi H, Hirose M, Mitsumori K
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Carcinogenesis. 2001 Apr;22(4):613-8. doi: 10.1093/carcin/22.4.613.
To cast light on whether xylazine hydrochloride (XZ), a veterinary medicine commonly used as a sedative agent for food-producing animals, has any promoting potential for thyroid carcinogenesis, the following studies were performed. In Experiment I, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ for 52 weeks with or without initiation with 2400 mg/kg N:-bis(2-hydroxypropyl)nitrosamine (DHPN). Focal follicular cell hyperplasias, adenomas and/or carcinomas were induced in the DHPN alone, XZ alone and DHPN+XZ groups, and the incidences and multiplicities of these lesions in the DHPN+XZ group were significantly increased as compared with the DHPN alone case. In Experiment II, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ and were examined for serum levels of triiodothyronine (T(3)), thyroxine (T(4)) and thyroid-stimulating hormone (TSH) at weeks 1, 2 and 4. In the XZ group, significant increase in thyroid weight and decrease in serum T(4) levels were observed at all time points. Serum T(3) and TSH levels were significantly decreased and increased, respectively, at week 1, but returned to within the control range thereafter. In Experiment III, male F344 rats received a diet containing 1000 or 0 p.p.m. XZ, they were examined for thyroid iodine uptake and organification of XZ after 1 and 2 weeks. The thyroidal iodine uptake per milligram of thyroid and the amount of iodine bound to 1 mg protein showed a tendency for decrease at week 1 and significant decrease at week 2. These results indicate that XZ has tumor-promoting effects on thyroid follicular cells, and suggest an involvement of alterations in thyroid-related hormone levels due to inhibition of thyroid iodine uptake and organification, resulting, provably, in serum TSH stimulation depending on continuous reduction of serum T(4) level through the feedback system in the pituitary-thyroid axis.
为了阐明盐酸赛拉嗪（XZ）——一种常用于食品生产动物的镇静剂兽药——是否具有促进甲状腺癌发生的潜在作用，进行了以下研究。在实验I中，雄性F344大鼠接受含1000或0 ppm XZ的饮食52周，同时给予或不给予2400 mg/kg N-双（2-羟丙基）亚硝胺（DHPN）启动处理。单独给予DHPN组、单独给予XZ组以及DHPN+XZ组均诱导出了局灶性滤泡细胞增生、腺瘤和/或癌，并且与单独给予DHPN的情况相比，DHPN+XZ组中这些病变的发生率和数量显著增加。在实验II中，雄性F344大鼠接受含1000或0 ppm XZ的饮食，并在第1、2和4周检测血清三碘甲状腺原氨酸（T(3)）、甲状腺素（T(4)）和促甲状腺激素（TSH）水平。在XZ组中，在所有时间点均观察到甲状腺重量显著增加以及血清T(4)水平降低。血清T(3)和TSH水平在第1周分别显著降低和升高，但此后恢复到对照范围内。在实验III中，雄性F344大鼠接受含1000或0 ppm XZ的饮食，在1周和2周后检测甲状腺碘摄取和XZ的有机化情况。每毫克甲状腺的甲状腺碘摄取量以及与1 mg蛋白质结合的碘量在第1周呈现下降趋势，在第2周显著下降。这些结果表明XZ对甲状腺滤泡细胞具有促肿瘤作用，并提示由于甲状腺碘摄取和有机化受到抑制，导致甲状腺相关激素水平发生改变，这可能通过垂体-甲状腺轴的反馈系统，随着血清T(4)水平持续降低，从而刺激血清TSH升高。
