Distinction between liver neoplasm promoting and syncarcinogenic effects demonstrated by exposure to phenobarbital or diethylnitrosamine either before or after N-2-fluorenylacetamide.

The effect on the liver carcinogenicity in rats of sequential administration of either phenobarbital (PB) or diethylnitrosamine (DEN) given either before or after N-2-fluorenylacetamide (FAA) was studied. DEN given in the drinking water either before or after dietary FAA enhanced liver carcinogenicity over that produced by FAA alone. In contrast, dietary PB produced enhancement only when given after FAA. Thus, the effects of DEN summate with those of FAA, whereas PB produces a promoting, but not syncarcinogenic, effect. The usefulness of reverse sequence protocols for distinguishing between initiation-promotion and syncarcinogenesis by sequentially administered chemicals is demonstrated.