SHORT COMMUNICATION Effect of the Peroxisome Proliferator LY171883 on Hepatocellular Replication in Female B6C3F1 Mice Effect of the Peroxisome Proliferator LY171883 on Hepa- tocellular Replication in Female B6C3F1 Mice. EACHO, P. I.,

LY171883 was shown to increase the incidence of hepatocel-lular carcinomas and other proliferative lesions in female B6C3F1 mice. This appeared to be unrelated to the induction of peroxisomal /S-oxidation. Experiments were conducted to de-termine the effect of dietary LY171883 for 7 or 94 days on hepatocellular replication using continuous 7-day infusion of bromodeoxyuridine. LY171883 caused a dose-related increase in hepatocyte replication during the first 7 days, with statistical significance in the two higher dose groups. There was no effect on hepatocyte replication after 94 days of treatment. Liver weight and peroxisomal /9-oxidation were increased in the two higher dose groups after 7 and 94 days, indicating there was not a gen-eral loss of hepatic responsiveness to LY171883. The data in-dicate that the hepatocarcinogenesis of LY171883 in female B6C3F1 mice is not associated with sustained replication in the general population of hepatocytes. It is possible that a mitogenic effect of LY171883 exerted on spontaneously initiated cells is involved in the development of the proliferative lesions; however, further work is needed to determine this. © 1992 society of LY171883 is a peroxisome proliferator which increased the incidence of hepatocellular carcinomas in B6C3F1 mice after 2 years administration in the diet (Bendele etal., 1990). The carcinogenicity was observed at doses that had little or no effect on peroxisomal /9-oxidation. A poor correlation between peroxisomal /9-oxidation and hepatocarcinogenesis was also observed in studies of di-(2-ethylhexyl)phthalate (DEHP) and Wy-14,643 in rats (Marsman et al., 1988). The greater carcinogenic potency of Wy-14,643 was associated with sustained stimulation of hepatocellular replication compared to the transient mitogenic effect of DEHP. Chronic elevation of cell replication by chemicals has been associated with an increased incidence of tumors in several organ