| ABSTRACT: |
|
Induction of cellular detoxification enzymes can increase
detoxification of carcinogens and reduce carcinogen-induced mutagenesis
and tumorigenesis. To determine if the dietary anticarcinogen ellagic acid
induced enzymes which detoxify xenobiotics and carcinogens, we examined
the effect of ellagic acid on the expression of the phase II
detoxification enzyme NAD(P)H:quinone reductase (QR). QR is induced by
xenobiotics and antioxidants interacting with the xenobiotic responsive
and antioxidant responsive elements of the 5' regulatory region of the QR
gene. Ellagic acid is structurally related to the antioxidants which
induce QR and we proposed that ellagic acid would induce QR expression
through activation of the antioxidant responsive element of the QR gene.
Rats fed ellagic acid demonstrated a 9-fold increase in hepatic and a
2-fold increase in pulmonary QR activity, associated with an 8-fold
increase in hepatic QR mRNA. To determine if this increase in QR mRNA was
due to activation of the antioxidant responsive element, transient
transfection studies were performed with plasmid constructs containing
various portions of the 5' regulatory region of the rat QR gene. These
transfection studies confirmed that ellagic acid induces transcription of
the QR gene and demonstrated that this induction is mediated through the
antioxidant responsive element of the QR gene. |