Kanno J, Onodera H, Furuta K, Maekawa A, Kasuga T, Hayashi Y
Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Toxicol Pathol. 1992;20(2):226-35. doi: 10.1177/019262339202000209.
Thyroid tumor-promoting effects of iodine deficiency and iodine excess were investigated in a rodent 2-stage model to estimate an optimal iodine intake range that would not effectively promote development of thyroid neoplasia. Six-week-old male F344 rats were given a single subcutaneous injection of 2,800 mg/kg body weight N-bis(2-hydroxypropyl)-nitrosamine (DHPN) or saline vehicle, maintained on Remington's iodine-deficient diet (21 +/- 2 ng/g iodide), and supplemented with various amounts of potassium iodide up to 260 mg/liter in drinking water to generate conditions ranging from severe iodine deficiency to severe iodine excess. In DHPN-treated rats, both conditions significantly increased thyroid follicular tumorigenesis. In DHPN-untreated rats, iodine deficiency produced diffuse thyroid hyperplasia, characterized by small follicles with tall epithelium and reduced colloid, together with a decrease in thyroxine (T4) and an increase in thyroid-stimulating hormone (TSH). On the other hand, iodine excess produced colloid goiter, characterized by large follicles with flat epithelium and abundant colloid admixed with normal or small-sized follicles lined by epithelium of normal height, together with normal serum T4 and slightly decreased TSH. These effects were directly proportional to the severity of iodine deficiency or extent of iodine excess and suggest that each condition has a different thyroid tumor promotion mechanism. Iodine intakes that showed the least tumor promotion were 2.6 and 9.7 micrograms/rat/day in this study. Promoting mechanisms and the problem of statistically estimating recommended daily iodine intake range are briefly discussed.
在啮齿动物两阶段模型中研究了碘缺乏和碘过量对甲状腺肿瘤的促进作用，以估计不会有效促进甲状腺肿瘤形成的最佳碘摄入量范围。给六周龄雄性F344大鼠皮下注射一次2800mg/kg体重的N-双（2-羟丙基）亚硝胺（DHPN）或生理盐水载体，维持在雷明顿碘缺乏饮食（21±2ng/g碘化物）上，并在饮用水中补充高达260mg/L的各种量的碘化钾，以产生从严重碘缺乏到严重碘过量的各种条件。在经DHPN处理的大鼠中，这两种情况均显著增加了甲状腺滤泡肿瘤的发生。在未经DHPN处理的大鼠中，碘缺乏导致弥漫性甲状腺增生，其特征为小滤泡、高柱状上皮和减少的胶体，同时甲状腺素（T4）减少，促甲状腺激素（TSH）增加。另一方面，碘过量导致胶体甲状腺肿，其特征为大滤泡、扁平上皮和与正常或小尺寸滤泡混合的丰富胶体，这些滤泡由正常高度的上皮排列，同时血清T4正常，TSH略有降低。这些作用与碘缺乏的严重程度或碘过量的程度成正比，表明每种情况都有不同的甲状腺肿瘤促进机制。在本研究中，显示出最少肿瘤促进作用的碘摄入量为2.6和9.7微克/大鼠/天。简要讨论了促进机制和统计学估计推荐每日碘摄入量范围的问题。
