INCREASING THE INTERVAL BETWEEN INITIATION AND THE ONSET OF EXPOSURE TO OROTIC-ACID DECREASES ITS PROMOTING EFFECT ON RAT-LIVER CARCINOGENESIS

The present study was designed to determine whether a delay in the sta rt of the promoting regimen after the administration of a carcinogen w ould influence the promoting efficacy of orotic acid on the developmen t of hepatocellular carcinoma in rats. Male Fischer 344 rats weighing 130-150 g were injected with a single dose of diethylnitrosamine (200 mg/kg body wt i.p.) then divided into 3 groups: groups 1 and 2 were gi ven semi-synthetic basal diet or the same diet containing 1% orotic ac id (OA) respectively starting 1 week after the carcinogen; group 3 rec eived the OA diet starting 5 weeks after the administration of diethyl nitrosamine. Animals from these 3 groups were sacrificed after 25, 32, 42 and 60 weeks of being fed their respective diets. The results indi cated that delaying the start of the OA diet after the carcinogen resu lted in about a 50% decrease in the incidence of hepatic nodules and/o r hepatocellular carcinomas at various time points during the experime nt. This decrease in promoting efficacy of OA was not apparently expla inable by lack of metabolic effects of OA, at least in terms of induct ion of nucleotide pool imbalance, a condition that appears to be impor tant for OA to exert its tumor promoting effects.