ELLAGIC ACID INDUCES TRANSCRIPTION OF THE RAT GLUTATHIONE S-TRANSFERASE-YA GENE

Induction of glutathione S-transferase (GST) enzymes can increase deto xification of carcinogens and reduce carcinogen-induced mutagenesis an d tumorigenesis. To determine if the anticarcinogen ellagic acid induc es cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of glutathione S-transferase-Ya. Ra ts fed ellagic acid demonstrated significant increases in total hepati c GST activity, hepatic GST-Ya activity and hepatic GST-Ya mRNA. To de termine if the observed increase in GST-Ya mRNA was due to ellagic aci d inducing transcription of the GST-Ya gene, transfection studies were performed with plasmid constructs containing various portions of the 5' regulatory region of the rat GST-Ya gene. The transfection studies demonstrated that ellagic acid increased GST-Ya mRNA by inducing trans cription of the GST-Ya gene and demonstrated that this induction is me diated through the antioxidant responsive element of the GST-Ya gene.