ABSTRACT
To define a link between the activation of PPAR and the phenomena of peroxisome proliferation and hepatocarcinogenesis, it is important to determine whether PPAR is directly responsible for the transcriptional activation of peroxisome-proliferatorresponsive genes. Candidate genes include those for the peroxisomal ß-oxidation enzymes and P450 4A1 (see above). Of special interest is the peroxisomal ßoxidation enzyme acyl-CoA oxidase, since this enzyme is responsible for the production of hydrogen peroxide and is therefore tentatively linked with cancer. If Reddy’s oxidative stress hypothesis of peroxisome-proliferator-induced carcinogenesis (see above) proves to be correct and PPAR directly regulates the transcription of the acyl-CoA oxidase gene, then this would provide a direct link with receptor activation and both peroxisome proliferation and cancer.
