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
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
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DOI：
10.1006/taap.1995.1025
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发表时间：
1995-02-01
影响因子：
3.8
通讯作者：
BIRNBAUM, LS
中科院分区：
文献类型：
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作者：
DILIBERTO, JJ;AKUBUE, PI;BIRNBAUM, LS
2,3,7,8-四氯二苯并-对二恶英（TCDD）的组织处置已被证明是剂量依赖性的大鼠。然而，没有报道的小鼠研究表明TCDD的剂量和时间依赖性分布以及靶组织对酶诱导的潜在敏感性。本研究的目的是确定剂量（0、0.1、1或10 μ g [H-3]TCDD/kg）和时间（治疗后7、14、21和35天）对小鼠组织分布（18个组织）和酶诱导（肝脏、皮肤、肺中CYP1A1和肝脏中CYP1A2）的影响。tcdd衍生放射性在各组织中的分布与剂量和时间有关，呈非线性分布。肝脏与脂肪组织的浓度比范围为0.6至3.1（第7天的低至高剂量），表明TCDD的处置存在剂量依赖性转移。与肝脏相反，在所有其他组织中，百分比剂量/g和百分比剂量/总组织的相对浓度随剂量增加而降低。第7天最低剂量时，所有组织均含有
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 mu g [H-3]TCDD/kg) and time (7, 14, 21, and 35 days posttreatment) 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