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2,3,7,8-四氯二苯并-对-二噁英在鸡胚中的肝微粒体乙氧芴香豆素O-脱乙基酶诱导能力及胞质Ah受体结合亲和力:四种鸟类的比较

Hepatic microsomal ethoxyresorufin O-deethylase-inducing potency in ovo and cytosolic Ah receptor binding affinity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: comparison of four avian species.

作者信息

Sanderson J T, Bellward G D

机构信息

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

出版信息

Toxicol Appl Pharmacol. 1995 May;132(1):131-45. doi: 10.1006/taap.1995.1094.

Abstract

The hepatic microsomal ethoxyresorufin O-deethylase (EROD)-inducing potency in ovo of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was determined in the domestic chicken (Gallus gallus), domestic pigeon (Columba livia), great blue heron, and double-crested cormorant. Dose-response curves were produced by injecting various doses of [3H]TCDD into the air sac of developing eggs during the latter third part of incubation. Hepatic EROD activities were measured in day-old hatchlings. Liver, yolk, and whole blood were analyzed for [3H]TCDD; no distributional differences among species were found. The ED50 for EROD induction was between one and two orders of magnitude lower in the chick (0.1 microgram/kg egg) than in the heron and cormorant (3-10 micrograms/kg egg). Consistent with this, the apparent affinity of TCDD for the hepatic cytosolic Ah receptor was about 15 times higher in the domestic chick (Kd = 0.75-1.6) than in the other avian species (pigeon, Kd = 11-14; heron, Kd = 10-20; cormorant, Kd = 12-16). Receptor binding affinities in the pigeon, heron, and cormorant were of the same order of magnitude as that reported for human placenta (D.K. Manchester, S.K. Gordon, C.L. Golas, E.A. Roberts, and A.B. Okey, 1987, Cancer Res. 47, 4861-4868). Subcutaneous edema was observed in TCDD-treated hatchlings of the chick, heron, and cormorant, but not of the pigeon, within the dose range examined. The laboratory dose-response relationships demonstrated that the heron and cormorant hatchlings that were exposed to TCDD and related chemicals in the Strait of Georgia (J.T. Sanderson, R.J. Norstrom, J.E. Elliott, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994b) J. Toxicol. Environ. Health 41, 245-263; and J.T. Sanderson, J.E. Elliott, R.J. Norstrom, P.E. Whitehead, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994a) J. Toxicol. Environ. Health 41, 435-450) had hepatic EROD activities at the lower end of the linear part of their respective dose-response curves. A further increase in levels of TCDD and related compounds in the environment would lead to a large increase in EROD activity and further increases in TCDD-induced toxicities, such as body weight loss and subcutaneous edema.

摘要

在家鸡(原鸡)、家鸽、大蓝鹭和双冠鸬鹚中测定了2,3,7,8-四氯二苯并-对-二恶英(TCDD)在卵内诱导肝微粒体乙氧基异吩恶唑酮-O-脱乙基酶(EROD)的能力。在孵化后期的三分之一阶段,将不同剂量的[3H]TCDD注入发育中鸡蛋的气囊,从而得出剂量-反应曲线。在一日龄雏鸟中测量肝EROD活性。分析肝脏、蛋黄和全血中的[3H]TCDD;未发现物种间的分布差异。雏鸡中EROD诱导的半数有效剂量(ED50)(0.1微克/千克蛋)比鹭和鸬鹚(3-10微克/千克蛋)低1至2个数量级。与此一致的是,在家鸡中TCDD对肝细胞质芳烃受体的表观亲和力(解离常数Kd = 0.75-1.6)比其他鸟类物种(家鸽,Kd = 11-14;鹭,Kd = 10-20;鸬鹚,Kd = 12-16)高约15倍。家鸽、鹭和鸬鹚中的受体结合亲和力与人类胎盘报道的亲和力处于同一数量级(D.K. 曼彻斯特、S.K. 戈登、C.L. 戈拉斯、E.A. 罗伯茨和A.B. 奥基,1987年,《癌症研究》47卷,4861-4868页)。在所研究的剂量范围内,在TCDD处理的雏鸡、鹭和鸬鹚雏鸟中观察到皮下水肿,但在家鸽雏鸟中未观察到。实验室剂量-反应关系表明,在佐治亚海峡接触TCDD及相关化学物质的鹭和鸬鹚雏鸟(J.T. 桑德森、R.J. 诺斯特罗姆、J.E. 埃利奥特、L.E. 哈特、K.M. 程和G.D. 贝尔沃德(1994b)《毒理学与环境卫生杂志》41卷,245-263页;以及J.T. 桑德森、J.E. 埃利奥特、R.J. 诺斯特罗姆、P.E. 怀特黑德、L.E. 哈特、K.M. 程和G.D. 贝尔沃德(1994a)《毒理学与环境卫生杂志》41卷,435-450页),其肝脏EROD活性处于各自剂量-反应曲线线性部分的下端。环境中TCDD及相关化合物水平的进一步升高将导致EROD活性大幅增加,并使TCDD诱导的毒性如体重减轻和皮下水肿进一步增加。

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