Huang Y, Harper P A, Okey A B
Department of Pharmacology, University of Toronto, ON, Canada.
Can J Physiol Pharmacol. 1995 Jan;73(1):18-26. doi: 10.1139/y95-003.
In liver of adult responsive C57BL/6J (B6) mice the aromatic hydrocarbon receptor (AHR) has high affinity for specific halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as well as nonhalogenated aromatic hydrocarbons (PAHs), such as benz[a]anthracene (BA) or 3-methylcholanthrene (MC). In livers of adult nonresponsive DBA/2J (D2) mice TCDD binds to a low-affinity variant form of AHR. Both TCDD and MC induce aryl hydrocarbon hydroxylase (AHH) in adult B6 mice, whereas adult D2 mouse liver is nonresponsive to MC. In fetal cell cultures derived from D2 mice AHH is induced by PAHs such as MC or BA, and these PAHs bind to cytosolic AHR (P.A. Harper, C.L. Golas, and A.B. Okey. Mol. Pharmacol. 40: 818-826, 1991). We compared AHR from fetal cell cultures with AHR from adult livers to determine whether there was some structural differences in receptors expressed in fetal cell culture that might permit cells from "nonresponsive" mice to respond to PAHs. The apparent molecular mass of AHR from cells cultured from 18-day fetuses is identical with that from adult liver within each strain of inbred mice tested (M(r) approximately 95 kDa in B6 and approximately 105 kDa in D2 mice). The AHR in D2 fetal cells was able to activate a transfected chloramphenicol acetyltransferase linked to a dioxin-responsive element nucleotide sequence (DRE-CAT) when the cells were treated with TCDD or MC. The potency of CAT expression in D2 fetal cells was similar to that in B6 fetal cells. Our data suggest that the responsiveness of fetal cells from "nonresponsive" mice is likely mediated by AHR in these cells but is not due to expression of a different allelic form of AHR ligand-binding subunit in fetal cells versus adult liver.
在成年有反应的C57BL/6J（B6）小鼠的肝脏中，芳烃受体（AHR）对特定的卤代芳烃，如2,3,7,8-四氯二苯并-对-二恶英（TCDD），以及非卤代芳烃（PAHs），如苯并[a]蒽（BA）或3-甲基胆蒽（MC），具有高亲和力。在成年无反应的DBA/2J（D2）小鼠的肝脏中，TCDD与AHR的低亲和力变体形式结合。TCDD和MC都能在成年B6小鼠中诱导芳烃羟化酶（AHH），而成年D2小鼠肝脏对MC无反应。在源自D2小鼠的胎儿细胞培养物中，AHH由PAHs如MC或BA诱导，并且这些PAHs与胞质AHR结合（P.A.哈珀、C.L.戈拉斯和A.B.奥基。《分子药理学》40: 818 - 826，1991）。我们比较了胎儿细胞培养物中的AHR与成年肝脏中的AHR，以确定在胎儿细胞培养物中表达的受体是否存在一些结构差异，这些差异可能使“无反应”小鼠的细胞对PAHs产生反应。在测试的每个近交系小鼠中，来自18天胎儿培养的细胞中的AHR的表观分子量与成年肝脏中的相同（B6小鼠中M(r)约为95 kDa，D2小鼠中约为105 kDa）。当用TCDD或MC处理细胞时，D2胎儿细胞中的AHR能够激活与二恶英反应元件核苷酸序列（DRE - CAT）相连的转染氯霉素乙酰转移酶。D2胎儿细胞中CAT表达的效力与B6胎儿细胞中的相似。我们的数据表明，“无反应”小鼠的胎儿细胞的反应性可能由这些细胞中的AHR介导，但不是由于胎儿细胞与成年肝脏中AHR配体结合亚基的不同等位基因形式的表达。
