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Abstract:The purpose of this study is to determine which combination of choline-deficient L-amino acid-defined (CDAA) diet as an endogenous factor, phenobarbital (PB) as an exogenous factor, and partial hepatectomy (PH), has the most promotive potential on hepatocellular foci formation initiated by diethylnitrosamine (DEN) in Fischer 344 rats. Experimental groups were treated with various combinations of DEN administration, PB administration, PH and CDAA diet. Formation of hepatocellular foci after eight weeks was examined by glutathione S-transferase placental form (GST-P) immunological staining. The focal area was markedly elevated in the CDAA+DEN group in comparison with the CDAA-only group or the CRF-1(basal diet)+DEN group. CDAA diet was shown to have a strong promotion effect on initiated cells by DEN. In the CRF-1+DEN-treated animals, the additional PB and PH treatment elevated the number of small foci, but slightly did the focal area. The effects of the additional PB and PH treatment in the CDAA+DEN-treated animals were not clear as they were masked by the strong promotion effect of CDAA diet. These results showed that CDAA diet was more promotive than the PB and PH treatment in inducing hepatocellular foci formation initiated by DEN in rats, and the additional PB and PH treatment could not be promotive furthermore in the CDAA+DEN-treated animals. (J Toxicol Pathol 2001; 14: 105-112)