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Prostaglandin Synthases Influence Thyroid Follicular Cell Proliferation But Not Carcinogenesis in Rats Initiated With N-Bis(2-hydroxypropyl)nitrosamine
- 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.
- Subjects :
- Male
Thyroid Hormones
medicine.medical_specialty
Nitrosamines
Time Factors
medicine.medical_treatment
Indomethacin
Thyroid Gland
Prostaglandin
Toxicology
medicine.disease_cause
Follicular cell
Dinoprostone
chemistry.chemical_compound
Antithyroid Agents
Thyroid-stimulating hormone
Internal medicine
Adenocarcinoma, Follicular
Follicular phase
medicine
Animals
Cyclooxygenase Inhibitors
Thyroid Neoplasms
Cell Proliferation
Prostaglandin-E Synthases
Sulfonamides
Antithyroid agent
Sulfadimethoxine
Thyroid
Organ Size
Immunohistochemistry
Rats, Inbred F344
Rats
Intramolecular Oxidoreductases
Endocrinology
medicine.anatomical_structure
chemistry
Cyclooxygenase 2
Carcinogenesis
Precancerous Conditions
Prostaglandin E
Subjects
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