A New Ligand for the Peroxisome Proliferator-Activated Receptor-{{gamma}} (PPAR-{{gamma}}), GW7845, Inhibits Rat Mammary Carcinogenesis

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A New Ligand for the Peroxisome Proliferator-Activated Receptor- ${gamma}$ (PPAR- ${gamma}$ ), GW7845, Inhibits Rat Mammary Carcinogenesis¹

Nanjoo Suh, Yongping Wang, Charlotte R. Williams, Renee Risingsong, Tona Gilmer, Timothy M. Willson and Michael B. Sporn²

Department of Pharmacology and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire 03755 [N. S., Y. W., C. R. W., R. R., M. B. S.], Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709 [T. G., T. M. W.]

We have tested a new ligand for peroxisome proliferator-activatedreceptor- ${gamma}$ , GW7845, as an inhibitor of experimental mammary carcinogenesis,using the classic rat model with nitrosomethylurea as carcinogen.Rats were first treated with a single dose of nitrosomethylurea(50 mg/kg body weight, i.p.). Starting 1 week later, they werefed GW7845, at either 60 or 30 mg/kg of diet, for 2 months.This agent significantly reduced tumor incidence, tumor number,and tumor weight at both doses. This is the first report ofthe use of a ligand for peroxisome proliferator-activated receptor- ${gamma}$ to prevent experimental breast cancer.

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