Journal Article

Prostaglandin Synthases Influence Thyroid Follicular Cell Proliferation But Not Carcinogenesis in Rats Initiated With N-Bis(2-hydroxypropyl)nitrosamine

Yoshio Ota, Toshio Imai, Mai Hasumura, Young-Man Cho, Shigeaki Takami, Toshifumi Oyamada, Masao Hirose, Akiyoshi Nishikawa and Kumiko Ogawa

in Toxicological Sciences

Volume 127, issue 2, pages 339-347
Published in print June 2012 | ISSN: 1096-6080
Published online March 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs097
Prostaglandin Synthases Influence Thyroid Follicular Cell Proliferation But Not Carcinogenesis in Rats Initiated With N-Bis(2-hydroxypropyl)nitrosamine

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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 PGE2, 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.

Keywords: sulfadimethoxine; indomethacin; nimesulide; thyroid follicular carcinoma; F344 rats

Journal Article.  4881 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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