We will develop a novel system for detecting chemicals which induce peroxisome proliferation. This system will consist of a human cell line which has been transfected with specific receptor and reporter gene constructs. Cells will be transfected with receptors for peroxisome proliferators derived from different species. The reporter gene (cDNA) is human cytochrome P450 which catalyzes formation of a fluorescent product. The reporter cDNA is coupled to a promoter linked to a peroxisome proliferator responsive element. The resulting assay system should be specific for peroxisome proliferators and easily amenable to automation for screening large numbers of chemicals.
