Effect of estragole on liver tumors glucocorticoid-mediated induction of liver-specific enzymes, and the activity of transcription factors FOXA and HNF4 in mouse and rat liver

The carcinogenic effects of estragole in mice of an earlier unexplored strain ICR have been studied. It has been shown that there is a distinct correlation between the extent of inhibition of glucocorticoid-mediated induction of tyrosine aminotransferase and tryptophan oxygenase after acute administration of estragole and the frequency of liver tumors after estragole exposure. Estragole inhibits the induction of these enzymes only in female mice, but not in male mice or in rats. DNA-binding activities of liver-enriched transcription factors were investigated on carcinogen-susceptible and resistant animals. Estragole decreases the HNF4 and FOXA DNA-binding activities only in susceptible female mice, but not in insusceptible male mice or in rats and does not influence the C/EBP and HNF1 activities. Pentachlorophenol, which prevents the hepatocarcinogenic effect of estragole, abolishes its inhibitory effect on tyrosine aminotransferase and tryptophan oxygenase glucocorticoid induction and restores the FOXA and HNF4 DNA-binding activities. The parallelism between the hepatocarcinogenic effects of estragole and the inhibition of FOXA and HNF4 DNA-binding activities serves as an additional argument for the involvement of these factors in the mechanisms of tumor suppression in the liver.