title: Animal models for human risk assessment: the peroxisome proliferator-activated receptor alpha-humanized mouse.
abstract: The hyperlipidemic fibrate drugs mediate their lipid-lowering effects through binding to and activating the peroxisome proliferator-activated receptor alpha (PPARalpha). PPARalpha ligands are potent hepatocarcinogens in rats and mice; after 11 months of feeding a fibrate drug, there is 100% incidence of adenomas and carcinomas. However, there is no evidence that humans chronically administered fibrates have increased cancer risk. Recent studies on PPARalpha-humanized mice have revealed a potential mechanism for the species differences in response to PPARalpha ligands. These models will be of great value in human risk assessment and in determining the mechanism of hepatocarcinogenesis.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. fjgonz@helix.nih.gov
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology*; D051379:Mice; D047493:PPAR alpha / Q000378:metabolism*; D018570:Risk Assessment / Q000379:methods*; D013045:Species Specificity
chemical_list: D047493:PPAR alpha