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Specificity of Co-Promoting Effects of Caffeine on Thyroid Carcinogenesis in Rats Pretreated with N-Bis(2-hydroxypropyl)nitrosamine

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan, College of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea

Akiyoshi Nishikawa

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan, nishikaw{at}nihs.go.jp

Kazushi Okazaki

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

Yasuki Kitamura

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

Keita Kanki

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

Kyong-Youl Lee

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan, College of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea

Takashi Umemura

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

Masao Hirose

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan

The specificity of copromotion effects of caffeine with known goitrogenic factors on thyroid carcinogenesis was examined in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 8 groups, each consisting of 10 animals, and received a single sc injection of 2,800 mg/kg DHPN. From one week after the DHPN initiation, they were given basal diet, iodine deficiency (ID) diet, 500 ppm phenobarbital (PB) solution or 1,000 ppm sulfadimethoxine (SDM) solution with or without 1,500 ppm caffeine feeding for 12 weeks. The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine. SDM drastically promoted thyroid carcinogenesis in association with increased serum TSH levels regardless of the caffeine treatment. Thyroid follicular carcinomas and adenomas were more frequently observed in the additional caffeine groups than in the ID alone groups. The incidence and multiplicity of focal thyroid follicular hyperplasias in the ID-treated groups were significantly (p < 0.05 and 0.01) elevated in the case of combination with caffeine. Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine. Serum thyroid hormone levels were significantly (p < 0.01) decreased by SDM but significantly (p < 0.05 or 0.01) increased by caffeine, PB or ID. Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.

Key Words: Thyroid carcinogenesis • caffeine • iodine deficiency • sulfonamide • phenobarbital.

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