Carcinogenesis, Vol. 21, No. 4, 707-713,
April 2000
© 2000 Oxford University Press
Carcinogenesis |
Dramatic synergism between excess soybean intake and iodine deficiency on the development of rat thyroid hyperplasia
Division of Pathology, National Institute of Health Sciences,1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 and
1 Showa Women's University, 1-7 Taishido, Setagaya-ku, Tokyo 154-8533, Japan
The effects of defatted soybean and/or iodine-deficient diet feeding were investigated in female F344 rats. Rats were divided into four groups, each consisting of 10 animals, and fed basal AIN-93G diet in which the protein was exchanged for 20% gluten (Group 1), iodine-deficient gluten (Group 2), 20% defatted soybean (Group 3) and iodine-deficient defatted soybean (Group 4). At week 10, relative thyroid gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 2 (15.5 ± 1.3) and 4 (81.7 ± 8.6) than in Group 1 (8.4 ± 2.0) and pituitary gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 3 (9.1 ± 0.6) and 4 (9.7 ± 1.5) than in Group 1 (6.5 ± 1.5). Serum biochemical assays revealed thyroxine to be significantly (P < 0.05) lower in Groups 2 and 4 than in Group 1. On the other hand, serum thyroid-stimulating hormone (TSH) was significantly (P < 0.01) higher in Groups 3 and 4 than in Group 1. This was particularly striking for TSH (ng/ml) at week 10 in Group 4 (126 ± 11) as compared with Groups 1 (4.36 ± 0.30), 2 (4.84 ± 0.80) and 3 (5.78 ± 0.80). Histologically, marked diffuse follicular hyperplasia of the thyroid was evident in Group 4 rats. Proliferating cell nuclear antigen labeling indices (%) were significantly higher (P < 0.05) in Groups 2 (4.8 ± 2.5) and 4 (13.2 ± 1.1) than in Group 1 (0.4 ± 0.5). Ultrastructurally, severe disorganization and disarrangement of mitochondria were apparent in thyroid follicular cells of Group 4. In the anterior pituitary, dilated rough surfaced endoplasmic reticulum and increased secretory granules were remarkable in this group. Our results thus strongly suggest that dietary defatted soybean synergistically stimulates the growth of rat thyroid with iodine deficiency, partly through a pituitary-dependent pathway.
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