THE DEVELOPMENT OF HEPATOCELLULAR-CARCINOMA IN INITIATED RAT-LIVER AFTER A BRIEF EXPOSURE TO OROTIC-ACID COUPLED WITH PARTIAL-HEPATECTOMY

Previous work from this laboratory has revealed that a minimum of 10-2 0 weeks of continuous exposure to 1% dietary erotic acid (OA) is neces sary for this regimen to exert a significant promoting effect on the c arcinogenic process in rat liver. The present study investigates the e ffect of partial hepatectomy (PH), given during a short-term exposure (4 weeks) to OA, on the development of hepatocyte nodules (HN) and hep atocellular carcinoma (HCC) initiated by diethylnitrosamine (DEN). Mal e Fischer 344 rats (130-150 g) were given a single dose of DEN (200 mg /kg body wt i.p.). Starting a week later they were fed either a semisy nthetic basal diet (BD) or the same diet containing 1% OA for 2 weeks; two-thirds PH was then performed followed by another 2 weeks of BD or OA diet respectively. At the end of this treatment some animals from both groups were killed while the rest were continued on BD and killed at 20 or 56 weeks thereafter. The results showed no difference betwee n the two groups in the incidence of gamma-glutamyltransferase-positiv e foci when rats were killed at 2 weeks after PH. However, 4 week expo sure to OA coupled with PH significantly enhanced the incidence of HN and HCC when this protocol was followed by 20 or 56 weeks of BD feedin g respectively, leading to 63% incidence of HCC in the OA-fed group, w hile no HCC was observed in control animals. It is concluded that a ty pe of stable or permanent change(s) ('imprinting' or 'memory effect') is induced in the initiated rat liver by this treatment, which imposes a promoting environment in the liver even after withdrawal of the pro moter.