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Promotion of colon tumors in C57BL/6J-APC(min)/+ mice by thiazolidinedione PPARgamma agonists and a structurally unrelated PPARgamma agonist.

Abstract
Thiazolidinedione PPARgamma agonists (troglitazone and rosiglitazone) were previously shown to promote colon tumor formation in C57BL/6J-APC(min)/+ mice, a model for human familial adenomatous polyposis. This study was conducted to determine if another thiazolidinedione PPARgamma agonist, pioglitazone, and a PPARgamma agonist structurally unrelated to the thiazolidinedione family, NID525, (a tetrazole-substituted phenoxymethylquinolone), would also promote colon tumors in this mouse model. Mice were treated in-feed with the thiazolidinediones troglitazone (150 mg/kg/day), rosiglitazone (20 mg/kg/day), or pioglitazone (150 mg/kg/day), or with NID525 (150 mg/kg/day) for 8 weeks. An increased incidence in colon tumors compared to controls was observed for all of the thiazolidinedione-treated groups as well as the NID525-treated group. These results indicate that the tumor-promoting effect of PPARgamma agonists in the colon of C57BL/6J-APC(min)/+ mice is likely related to the pharmacological activity of this group of drugs and not the thiazolidinedione structure.
AuthorsMichael V Pino, Michael F Kelley, Zaid Jayyosi
JournalToxicologic pathology (Toxicol Pathol) 2004 Jan-Feb Vol. 32 Issue 1 Pg. 58-63 ISSN: 0192-6233 [Print] United States
PMID14713549 (Publication Type: Journal Article)
Chemical References
  • Carcinogens
  • Chromans
  • Hypoglycemic Agents
  • NID525
  • Quinolines
  • Receptors, Cytoplasmic and Nuclear
  • Tetrazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Troglitazone
  • Pioglitazone
Topics
  • Adenocarcinoma (chemically induced, genetics, pathology)
  • Adenoma (chemically induced, genetics, pathology)
  • Animals
  • Carcinogens (toxicity)
  • Chromans (chemistry, toxicity)
  • Colonic Neoplasms (chemically induced, genetics, pathology)
  • Gene Expression (drug effects)
  • Genes, APC
  • Hypoglycemic Agents (chemistry, toxicity)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Pioglitazone
  • Quinolines (chemistry, toxicity)
  • Receptors, Cytoplasmic and Nuclear (agonists, antagonists & inhibitors)
  • Rosiglitazone
  • Structure-Activity Relationship
  • Tetrazoles (chemistry, toxicity)
  • Thiazolidinediones (chemistry, toxicity)
  • Transcription Factors (agonists, antagonists & inhibitors)
  • Troglitazone

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