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Tumor-Promoting Effects of Both Iodine Deficiency and Iodine Excess in the Rat Thyroid

Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Yushima 1–5–45, Bunkyo-ku, Tokyo 113

Hiroshi Onodera

Division of Pathology, Biological Safety Research Center, National Institute of Hygienic Sciences, Kamiyoga 1–18–1, Setagaya-ku, Tokyo 158, Japan

Kyoko Furuta

Division of Pathology, Biological Safety Research Center, National Institute of Hygienic Sciences, Kamiyoga 1–18–1, Setagaya-ku, Tokyo 158, Japan

Akihiko Maekawa

Division of Pathology, Biological Safety Research Center, National Institute of Hygienic Sciences, Kamiyoga 1–18–1, Setagaya-ku, Tokyo 158, Japan

Tsutomu Kasuga

Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University, Yushima 1–5–45, Bunkyo-ku, Tokyo 113

Yuzo Hayashi

Division of Pathology, Biological Safety Research Center, National Institute of Hygienic Sciences, Kamiyoga 1–18–1, Setagaya-ku, Tokyo 158, Japan

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 cpithelium 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 µg/rat/day in this study. Promoting mechanisms and the problem of statistically estimating recommended daily iodine intake range are briefly discussed.

Key Words: Neoplasia • neoplasms • hyperplasia • thyroid-stimulating hormone • thyroxine • pituitary-thyroid axis • Wolff-Chaikoff effect • escape phenomenon • recommended iodine intake

Toxicologic Pathology, Vol. 20, No. 2, 226-235 (1992)
DOI: 10.1177/019262339202000209


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				J. Kanno, T. Nemoto, T. Kasuga, and Y. Hayashi Effects of a Six-Week Exposure to Excess Iodide on Thyroid Glands of Growing and Nongrowing Male Fischer-344 Rats Toxicol Pathol, January 1, 1994; 22(1): 23 - 28. [Abstract] [PDF]