Barch D H, Rundhaugen L M
Department of Medicine, Lakeside Veterans Affairs Medical Center, Chicago, IL.
Carcinogenesis. 1994 Sep;15(9):2065-8. doi: 10.1093/carcin/15.9.2065.
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.
诱导细胞解毒酶可增强致癌物的解毒作用，并减少致癌物诱导的诱变和肿瘤发生。为了确定膳食抗癌剂鞣花酸是否能诱导对外源生物和致癌物进行解毒的酶，我们研究了鞣花酸对II相解毒酶NAD(P)H:醌还原酶（QR）表达的影响。QR由外源生物和抗氧化剂诱导产生，这些物质与QR基因5'调控区的外源生物反应元件和抗氧化反应元件相互作用。鞣花酸在结构上与诱导QR的抗氧化剂相关，我们推测鞣花酸会通过激活QR基因的抗氧化反应元件来诱导QR表达。喂食鞣花酸的大鼠肝脏中QR活性增加了9倍，肺中增加了2倍，同时肝脏中QR mRNA增加了8倍。为了确定QR mRNA的这种增加是否是由于抗氧化反应元件的激活，我们用含有大鼠QR基因5'调控区不同部分的质粒构建体进行了瞬时转染研究。这些转染研究证实鞣花酸可诱导QR基因转录，并表明这种诱导是通过QR基因的抗氧化反应元件介导的。
