Comparison of the effects of nafenopin on hepatic peroxisome proliferation and replicative DNA synthesis in the rat and Syrian hamster

Abstract

Male Sprague-Dawley rats were fed control or 0.1% nafenopin diet and male Syrian hamsters were fed control or 0.25% nafenopin diet for periods of 7 and 54 days. Nafenopin treatment produced a sustained increase in liver weight and induction of hepatic peroxisomal and microsomal fatty acid-oxidizing enzyme activities, with a greater effect being observed in the rat. Replicative DNA synthesis was studied by implanting osmotic pumps containing [ 3H]thymidine during study days 0–7 and 47–54. Cell replication, determined either as the hepatocyte labelling index or by incorporation of radioactivity into liver whole homogenate DNA, was increased in rats given nafenopin for 7 and 54 days. In contrast to the rat, no significant effect on replicative DNA synthesis was observed in the Syrian hamster. These results provide further evidence for species differences in hepatic peroxisome proliferation, with the Syrian hamster being less responsive than the rat. Furthermore, while peroxisome proliferators produce hyperplasia in rat and mouse liver, these data suggest that they may not have any marked effect on hepatic replicative DNA synthesis in the Syrian hamster.