ABSTRACT
Peroxisome proliferators (PPs) are a diverse class of chemicals that share the common ability to induce the proliferation of hepatic peroxisomes in rodents and which constitute a discrete class of rodent hepatocarcinogens. This chapter deals with rodent-based systems for assaying the toxicity and carcinogenic potential of PPs, and discusses the relevence of these for predicting human carcinogenicity. Mechanistic information is crucial both to the development and evaluation of predictive tests for PP-induced hepatocarcinogenesis in the rodent and for the extrapolation to humans for risk-assessment purposes. The peroxisome proliferation phenomenon in rodents is characterized by marked hepatomegaly due largely to hepatocellular hypertrophy and hyperplasia. The determination of chemically stimulated replicative DNA synthesis is best performed using surgically implanted osmotic pumps containing a DNA precursor, such as 3 H-thymidine or bromodeoxyuridine. In vitro experiments using primary cultures of hepatocytes usually faithfully mimic in vivo experiments in respect to potency rankings and species differences.
