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Rat Liver Foci Bioassay

This article is a review of the rat liver foci bioassay which is an initiation/promotion assay that utilizes preneoplastic foci of hepatocytes possessing altered enzymatic activity and altered cellular constituents as indicators of carcinogenesis. Rat liver tumor promoters that have been employed in the assay include: (1) a low level of 2-acetylaminofluorene in the diet, (2) phenobarbital in the diet and drinking water and (3) a choline deficient diet. Camma-glutamyl transpeptidase-positive, and adenosine triphosphatase, and glucose-6-phosphatase-defi-cient foci are used to indicate the initiation of cancer and are reviewed with respect to their relationship to cancer. Partial hepatectomy at the time of initiation increases the sensitivity of the assay to dialkylnitrosamines and chemicals which are otherwise negative in rat liver. The protocols being developed by the Health Effects Research Laboratory in Cincinnati include: (1) partial hepatectomy either 18 hours prior to or 14 days after administering the chemical under test, (2) phenobarbital promotion and (3) using gamma-glutamyl transpeptidase-positive foci as the indicator of carcinogenesis. The article also reviews the rat liver foci bioassay as a component of the Carcinogenesis Testing Matrix for tier II where it will be employed to confirm the carcinogenic hazard associated with environmental samples containing complex mixtures.