Effects of Peroxisome Proliferators in Vivo and in Primary Hepatocyte Cultures from Chinese and Syrian Hamsters
A number of chemicals have been shown to produce liver enlargement and hepatic peroxisome proliferation in rodents and certain of these compounds have also been shown to increase the incidence of liver tumours. Whilst a precise relationship between peroxisome proliferation and liver tumour formation remains to be established, species differences may be important in extrapolating rodent findings to man. In this study the effect of di-(2-ethylhexyl) phthalate, mono-(2-ethylhexyl) phthalate (MEHP) and clofibric acid in Chinese and Syrian hamsters were compared. After oral administration for 14 days all three compounds produced liver enlargement and induction of peroxisomal enzyme activities in both species but the response was more marked in Chinese hamsters. In cell culture studies both MEHP and clofibric acid produced a greater induction of peroxisomal β-oxidation in hepatocytes from Chinese than from Syrian hamsters. These results thus demonstrate a species difference in the magnitude of response to certain peroxisome proliferators after oral administration between Chinese and Syrian hamsters. As this difference was also observed in vitro the results suggest that intrahepatic factor(s), which are retained in cell culture, were primarily responsible for the observed species difference.
(Supported by UK Ministry of Agriculture, Fisheries and Food.)