Hepatomegaly is an early biomarker for hepatocarcinogenesis induced by peroxisome proliferators

The relationship between hepatomegaly and the hepatocarcinogenesis associated with by peroxisome proliferators was examined. (1) Male F-344 rats were maintained on diets containing clofibrate, ciprofibrate, nafenopin, gemfibrozil, Wy-14, 643, di(2-ethylhexyl)phthalate (DEHP), or di(2-ethylhexyl)adipate (DEHA) at carcinogenic doses for 1 week. A close correlation between relative liver weights and hepatocarcinogenicity was observed (r = 0.910). (2) Administration of perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), simfibrate, or DL-040, for which hepatocarcinogenicity is not known, resulted in hepatomegaly in all treated groups, this being especially marked in the PFOA case. Therefore, PFOA may have strong hepatocarcinogenic potential. (3) Administration of the antioxidants butylated hydroxyanisole (BHA) or vitamin E (VE) did not affect the hepatomegaly induced by DEHP. These results suggest that the hepatomegaly may be an early biomarker for prediction of the potential hepatocarcinogenicity of peroxisome proliferators. However, this requires further clarification in terms of its relation to the oxidative stress thought to be involved in peroxisome proliferator-induced hepatocarcinogenesis.