The carcinogenic effects of
estragole in mice of the earlier unexplored strain ICR has 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 trypthophan
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 and rats.
DNA-binding activities of liver-enriched
transcription factors were investigated on
carcinogen-susceptible and -resistant animals.
Estragole decreases the HNF4 (hepatic nuclear factor 4) and FOXA
DNA-binding activities only in susceptible female mice, but not in nonsusceptible male mice and 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 trypthophan
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.