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

Authors :
Toshio Imai
Yoshio Ota
Akiyoshi Nishikawa
Mai Hasumura
Young-Man Cho
Masao Hirose
Shigeaki Takami
Toshifumi Oyamada
Kumiko Ogawa
Source :
Toxicological Sciences. 127:339-347
Publication Year :
2012
Publisher :
Oxford University Press (OUP), 2012.

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.

Details

ISSN :
10960929 and 10966080
Volume :
127
Database :
OpenAIRE
Journal :
Toxicological Sciences
Accession number :
edsair.doi.dedup.....786225558f5395c5d125aefe4ff91afa
Full Text :
https://doi.org/10.1093/toxsci/kfs097