Dose-Response Relationships of Tissue Distribution and Induction of Cyp1A1 and Cyp1A2 Enzymatic Activities Following Acute Exposure to 2,3,7,8-Tetrachlorodibenzo- p-Dioxin (TCDD) in Mice

Tissue disposition of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) has been shown to be dose-dependent in rats. However, no reported studies in mice have demonstrated dose- and time-dependent distribution of TCDD and the potential sensitivities of target tissues to enzyme induction. The objectives of this study were to determine in mice the effects of dose (0, 0.1, 1, or 10 μg [ 3H]TCDD/kg) and time (7, 14, 21, and 35 days post-treatment) on tissue distribution (18 tissues) and enzyme induction (CYP1A1 in liver, skin, and lung and CYP1A2 in liver). Distribution of TCDD-derived radioactivity in all tissues was dose- and time-dependent with nonlinear distribution. Liver-to-adipose tissue concentration ratios range from 0.6 to 3.1 (low to high dose at Day 7) demonstrating a dose-dependent shift in the disposition of TCDD. In contrast to liver, relative concentrations of percentage dose/g and percentage dose/total tissue decreased with increasing doses in all other tissues. At Day 7 and lowest dose, all tissues contained