title: Specificity of co-promoting effects of caffeine on thyroid carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine.
abstract: 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.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Son
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Kazushi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Keita
authors.initials: K
authors.lastname: Kanki
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: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D002110:Caffeine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D008297:Male; D009602:Nitrosamines / Q000633:toxicity; D010634:Phenobarbital / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013412:Sulfadimethoxine / Q000633:toxicity; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013972:Thyrotropin / Q000097:blood
chemical_list: D000890:Anti-Infective Agents; D002273:Carcinogens; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D009602:Nitrosamines; D013412:Sulfadimethoxine; D002110:Caffeine; C012457:diisopropanolnitrosamine; D013972:Thyrotropin; D010634:Phenobarbital