Antioxidant response element-mediated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induction of human NAD(P)H:quinone oxidoreductase 1 gene expression

Antioxidant response element (ARE) is required for high basal expression of the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in tumor cells and its induction in response to P-naphthoflavone and phenolic antioxidants. In this study, we have demonstrated that ARE also is required for induction of human NQO1 gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The various results suggest an alternate pathway for TCDD induction of human NQO1 gene expression. This pathway is independent of xenobiotic response element (XRE) and aromatic hydrocarbon (Ah) receptor. It is presumed that TCDD-induced expression of CYP1A1 leads to increased oxidative stress, resulting in transcriptional activation and/or modification of ARE-binding factors and increased expression of the human NQO1 gene. (C) 1999 Elsevier Science Inc.