INDUCTION OF HEPATIC PEROXISOME PROLIFERATION IN NONRODENT SPECIES, INCLUDING PRIMATES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 114  (1) , 171-183
Abstract
Administration to rodents of a variety of structurally diverse chemicals possessing hypotriglyceridemic properties results in hepatomegaly, the induction of hepatic peroxisome (microbody) proliferation, and the development of hepatocellular carcinomas. Persistent proliferation of peroxisomes may serve as an endogenous initiator of neoplastic transformation in liver by increasing the intracellular production of H2O2 by the peroxisomal oxidase(s). A study was made to determine whether hepatic peroxisome proliferation can be induced in cats, chickens, pigeons and 2 spp. of monkeys (rhesus and cynomolgus). The hypolipidemic drug ciprofibrate (2-[4-(2,2-dichlorocylcopropyl)phenoxyl]2-methylpropionic acid) induced peroxisome proliferation in the livers of cats (dose, > 40 mg/kg body wt for 4 wk); chickens (dose > 25 mg/kg body wt for 4 wk), rhesus monkeys (50-200 mg/kg body wt for 7 wk) and cynomolgus monkeys (400 mg/kg body wt for 4 wk). In all 5 spp. examined, a marked but variable increase in the activities of peroxisomal catalase, carnitine acetyltransferase, heat-labile enoyl-CoA hydratase, and the fatty acid .beta.-oxidation system was observed. Peroxisome proliferation may be induced in the livers of several species and it is possibly a dose-dependent, but not a species-specific, phenomenon.

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