title: Prostaglandin synthases influence thyroid follicular cell proliferation but not carcinogenesis in rats initiated with N-bis(2-hydroxypropyl)nitrosamine.
abstract: To clarify roles of prostaglandin synthases in rat thyroid follicular carcinogenesis, effects of an antithyroid agent, sulfadimethoxine (SDM), and two prostaglandin H synthase (COX) inhibitors, indomethacin and nimesulide, on prostaglandin synthase expression, follicular cell proliferation, and tumor induction in thyroids of rats with or without N-bis(2-hydroxypropyl)nitrosamine (DHPN) initiation were examined. In experiment 1, F344 male rats were allowed free access to drinking water containing SDM (0.1%), SDM + indomethacin (0.0025% in diet), or SDM + nimesulide (0.04% in diet) for 4 weeks. Both COX inhibitors suppressed goitrogenic activity of SDM, but they did not significantly affect microsomal prostaglandin E synthase-2 (mPGES-2) expression levels enhanced by SDM. In experiment 2, all rats received an injection of DHPN (2800 mg/kg body weight), and starting 1 week later, they were treated as in experiment 1 for 4 or 10 weeks. Cell proliferation was suppressed or showed a tendency for suppression by the COX inhibitors in the follicular preneoplastic/neoplastic lesions and surrounding parenchyma, and this was obviously thyroid stimulating hormone independent at least at week 4. However, neither of the COX inhibitors altered the incidence or multiplicity of preneoplastic/neoplastic lesions. Immunohistochemistry revealed significant reduction and elevation of COX-2 and mPGES-2 expression, respectively, in the lesions, but these were also not changed by the COX inhibitors. These results suggest that COX-2 and PGES, and in turn PGE(2), might play important roles in follicular cell proliferation but do not affect tumor induction in this rat thyroid carcinogenesis model. Further studies are needed to clarify the significance of the reduction of COX-2 expression in preneoplastic/neoplastic lesions.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ota
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Mai
authors.initials: M
authors.lastname: Hasumura
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Cho
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Takami
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Oyamada
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D018263:Adenocarcinoma, Follicular; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D000071876:Prostaglandin-E Synthases; D051381:Rats; D011916:Rats, Inbred F344; D013412:Sulfadimethoxine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
chemical_list: D013956:Antithyroid Agents; D016861:Cyclooxygenase Inhibitors; D009602:Nitrosamines; D013449:Sulfonamides; D013963:Thyroid Hormones; D013412:Sulfadimethoxine; C012457:diisopropanolnitrosamine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; C012655:nimesulide; D007213:Indomethacin