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Promotion of Colon Tumors in C57BL/6J-APCmin/+ Mice by Thiazolidinedione PPAR Agonists and a Structurally Unrelated PPAR Agonist
Michael V. Pino
Aventis Inc, Drug Safety Evaluation, Bridgewater, New Jersey, USA, michael. pino{at}aventis.com
Michael F. Kelley
Aventis Inc, Drug Safety Evaluation, Bridgewater, New Jersey, USA
Zaid Jayyosi
Aventis Inc, Drug Safety Evaluation, Bridgewater, New Jersey, USA
Thiazolidinedione PPAR agonists (troglitazone and rosiglitazone) were previously shown to promote colon tumor formation in C57BL/6JAPC min/+ mice, a model for human familial adenomatous polyposis. This study was conducted to determine if another thiazolidinedione PPAR agonist, pioglitazone, and a PPAR 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 PPAR agonists in the colon of C57BL/6J-APCmin/+ mice is likely related to the pharmacological activity of this group of drugs and not the thiazolidinedione structure.
Key Words: Thiazolidinedione • PPAR gamma agonist • colon tumors • APC min mouse • adenomatous polyposis coli gene.
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Toxicologic Pathology, Vol. 32, No. 1,
58-63 (2004)
DOI: 10.1080/01926230490261320
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