The Lack of AHD4 Induction by TCDD in Corneal Cells May Involve Tissue-Specific Regulatory Proteins

The AHenzyme is encoded by a single gene which is a member of the mouse aromatic hydrocon [Ah] battery. The latter contains at least six genes that are coordinately inducen liver cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Nebert et al., 1993). These lude two P450 genes, Cyplal and Cypla2, and four Phase II genes, NA(P)H:me- nadionxidoreductase (Nqo1); aldehyde dehydrogenase (Ahd4); UDP glucuronosyltrans- feraseitUgtl*a6); and glutathione transferase (Gstal). Induction of all six [Ah] genes by TCDD rires both the Ah receptor (AHR) and Ah receptor nuclear translocator protein (ARNT)nd operates via nuclear translocation followed by binding to aromatic hydrocarbon response dementAhREs). Increased expression of the Phase II genes serves as a defense mechan against oxidative stress caused by endogenous and exogenous stimuli (Shert et al., 1995; Vasiliou et al., 1995). This up-regulation occurs via the electrophile rensive eement (EpRE; Jaiswal, 1994). AhREs and EpRE are present and functional in the 5019; flanking region of the mouse Ahd4 gene (Vasiliou et al., 1997).