Peroxisome proliferator-activated receptor-alpha and the pleiotropic responses to peroxisome proliferators.

Abstract

Peroxisome proliferators (PPs) form a discrete class of rodent non-genotoxic hepatocarcinogens (see Stringer, 1992 for review). These chemicals, which include industrially and pharmaceutically important compounds such as chlorinated solvents, plasticisers and hypolipidaemic drugs, have been the subject of intensive study over a number of years. Generally, following administration of PPs rats and mice undergo a range of responses including proliferation of peroxisomes in the liver and kidney, induction of certain hepatic enzymes, and liver enlargement. Although the vast majority of PPs are nongenotoxic by in vivo and in vitro criteria (reviewed in Ashby et al., 1994), these compounds cause the development of hepatocellular carcinomas when administered continually to rats and mice.