The significance of in vitro studies on peroxisome proliferation

Peroxisome proliferation in rodents is associated with hepatocarcinogenicity. This association has led to increased interest in the phenomenon and to the search for in vitro tests to detect peroxisome proliferators and to study the mechanisms by which proliferation occurs. Primary cultures of adult rat hepatocytes provide such a system: peroxisomal enzymes, cytochrome P-452 and replicative DNA synthesis may all be induced and the response to treatment with many peroxisome proliferators is observed in a manner similar to that in the liver in vivo. Cultured hepatocytes, therefore, provide an optimal system: (i) to screen for potential peroxisome proliferators; (ii) to study structure-activity relationships; (iii) to investigate species differences in the effects of peroxisome proliferators on hepatocytes; and (iv) to study the molecular mechanisms underlying peroxisome proliferation and its relationship to tumour formation.