SUMMATIONAL EFFECT OF THREE DIFFERENT HEPATOPROMOTERS IN RATS AFTER INITIATION WITH DIETHYLNITROSAMINE

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The effects of sequential administrations of three different hepatopromoters: 0.05% phenobarbital (PB), 0.25% 3-(3,5-dichlorophenyl)-5, 5-dimethyloxazoline-dione-2,4 (DDOD), and 0.05% polychlorinated biphenyls (PCB), in the diet on hepatocarcinogenesis were examined in male F344 rats after initiation by intraperitoneal injection of diethylnitrosamine (DEN) at 200 mg/kg body weight. The hepatopromoters were administered sequentially for 2 week periods in various combinations, and partial hepatectomy was performed at the end of week 3 to increase the induction of hyperplastic lesions (hyperplastic foci and nodules). A single administration of DEN followed by basal diet for 2 weeks and then promoter resulted in hyperplastic lesions, which showed time-dependent increase in their number and area up till the final sacrifice at week 8. All the three hepatopromoters coused increase of liver weight and promoted the development of hyperplastic lesions in groups given initiation with DEN. Summational effects of the promoters were seen when two or all of the three were administered together. No antagonistic effects among the three hepatopromoters were observed. These results suggest that effects of various hepatopromoters on hepatocarcinogens are summational when administered sequentially.
1984-03-26