Studies on the Effects of Peroxisome Proliferators as Novel Ca2+ Mobilizing Agents Using Indo-1-Loaded Hepatocytes

Abstract

A class of chemically diverse rodent hepatocarcinogens has been identified which induces the proliferation of both hepatocytes and peroxisomes, the hepatocellular organelles involved in fatty acid metabolism (Reddy and Rao, 1986; Rao and Reddy, 1987). These agents include pharmaceutical compounds, such as hypolipidemic drugs, as well as industrial plasticizing agents and pesticides. Collectively, these chemicals have been termed peroxisome proliferating agents (PPA). Despite the carcinogenicity of these agents, they fail to interact with DNA (Goel et al., 1985; Schiestl and Reddy, 1990). Therefore, the PPA constitute a distinct class of non-genotoxic hepatocarcinogens. To date, no definitive evidence exists to explain the carcinogenicity or tumour promoting capacity of the PPA. However, the ability of the PPA to induce hepatocyte proliferation, oxidative stress (as a result of peroxisomal proliferation), and to also bind a novel steroid-like receptor (Issemann and Green, 1990), have all been suggested to play an important role in the carcinogenicity of the PPA. It is likely, however, that all of these components play an important role in the carcinogenicity and tumour promoting capacity of the PPA.