title: Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.
abstract: The combined effects of caffeine (1,3,7-trimethylxanthine) with iodine deficiency (ID) were examined in a rat two-stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male F344 rats were divided into 6 groups each consisting of 10 animals, and received a single s.c. injection of 2800 mg/kg DHPN. From 1 week after the DHPN initiation, the rats were respectively fed a basal diet in which the protein was exchanged for 20% gluten, containing 1500 ppm caffeine + ID, 300 ppm caffeine + ID, 60 ppm caffeine + ID, 1500 ppm caffeine or ID or a basal diet alone for 12 weeks. Relative thyroid weights were significantly (P < 0.05) increased due to the development of proliferative lesions induced by the ID diet as compared to the DHPN-alone group value, which was enhanced by caffeine, albeit without statistical significance. Relative pituitary weights were significantly (P < 0.05) increased with 300 or 1500 ppm caffeine + ID as compared to the DHPN-alone group value. Serum thyroid stimulating hormone (TSH) levels were slightly increased by ID, an effect which was further enhanced by 300 or 1500 ppm caffeine. Serum thyroxine (T(4)) levels were slightly increased by caffeine or ID alone, but decreased by caffeine with ID. Histopathologically, thyroid follicular carcinomas were found only in the 1500 ppm caffeine + ID group, although thyroid follicular adenomas were detected in all the ID-treated groups. The multiplicity of focal thyroid follicular hyperplasias was significantly (P < 0.05) increased by 1500 ppm caffeine. These results indicate that caffeine may synergistically promote thyroid carcinogenesis with ID partially through a pituitary-dependent pathway in rats, implying the possible implication of routine caffeine intake in the promotion of thyroid carcinogenesis.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan. nishikaw@nihs.go.jp
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Son
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Keita
authors.initials: K
authors.lastname: Kanki
authors.forename: Kazushi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Kyong-Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Takashi
authors.initials: T
authors.lastname: Umemura
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000139:chemically induced / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000378:metabolism; D002110:Caffeine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003043:Cocarcinogenesis; D004347:Drug Interactions; D005260:Female; D007455:Iodine / Q000172:deficiency*; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013974:Thyroxine / Q000097:blood
chemical_list: D000891:Anti-Infective Agents, Local; D002273:Carcinogens; D000697:Central Nervous System Stimulants; D009602:Nitrosamines; D002110:Caffeine; C012457:diisopropanolnitrosamine; D007455:Iodine; D013974:Thyroxine