DIELDRIN INDUCES CYTOSOLIC [3H]7,12-DIMETHYLBENZ[a]ANTHRACENE BINDING BUT NOT MULTIDRUG RESISTANCE PROTEINS IN RAINBOW TROUT LIVER

DIELDRIN INDUCES CYTOSOLIC [3H]7,12-DIMETHYLBENZ[a]ANTHRACENE BINDING BUT NOT MULTIDRUG RESISTANCE PROTEINS IN RAINBOW TROUT LIVER
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狄氏剂在虹鳟鱼肝脏中诱导胞质 [3H]7,12-二甲基苯并[a]蒽结合,但不诱导多药耐药蛋白

DOI:
10.1080/00984100050027824
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发表时间:
2000
期刊:
Journal of Toxicology and Environmental Health, Part A
影响因子:
--
通讯作者:
Lee A. Courtney
Lee A. Courtney
中科院分区:
--
文献类型:
--
作者:
Lawrence R. Curtis;Michael J. Hemmer;Lee A. Courtney

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先前的研究表明,虹鳟鱼每天喂食 0.3?0.4 mg 狄氏剂/kg,连续 9?12 周,单剂量的[14C]狄氏剂或[3H]7,12-二甲基苯并[a]蒽 (DMBA) 的胆汁排泄分别被刺激高达 700% 和 300%。这不能通过蛋白质印迹定量的肝微粒体异生物质代谢酶活性增加或六种细胞色素 P-450 同工酶中任何一种的数量增加来解释。据推测,刺激的排泄是通过诱导以下物质来解释的:(1) 促进 DMBA 细胞内运输至代谢位点的胞质结合蛋白,或 (2) 将异生代谢物从肝脏转运至胆汁的 ATP 依赖性蛋白。在喂食狄氏剂的鱼的肝细胞质中,15 和 60 nmol [3H]DMBA/mg 蛋白质的结合增加了约 200%。 50 倍摩尔过量的未标记 DMBA 使对照和狄氏剂喂养鱼的细胞质中 15 nmol [3H]DMBA/mg 蛋白质的结合(非特异性结合)降低了相同量,表明狄氏剂诱导了特异性结合。使用多药耐药 (MDR) 蛋白单克隆抗体 C494、C219 和 JSB-1 以及多克隆抗体 MDR Ab-1 处理对照鱼和狄氏剂喂养鱼的肝脏切片。对照鱼和狄氏剂喂养鱼的胆小管附近的免疫组织化学染色的光密度没有显着差异。狄氏剂喂养的虹鳟鱼细胞质中外源物质结合能力的诱导至少部分解释了用这种环二烯杀虫剂预处理的鱼中 DMBA 分布的改变。
Previously it was demonstrated that biliary excretion of a single dose of [14C]dieldrin or [3H]7,12-dimethylbenz[a]anthracene (DMBA) was stimulated up to 700% and 300%, respectively, in rainbow trout fed 0.3?0.4 mg dieldrin/kg/d for 9?12 wk. This was not explained by increased activities of hepatic microsomal xenobiotic-metabolizing enzymes or increased amounts of any of six cytochrome P-450 isozymes quantitated by Western blots. It was hypothesized that stimulated excretion was explained by induction of (1) cytosolic binding proteins that facilitated intracellular trafficking of DMBA to sites of metabolism, or (2) ATP-dependent proteins that transport xenobiotic metabolites from liver to bile. Binding of 15 and 60 nmol [3H]DMBA/mg protein increased about 200% in hepatic cytosol from dieldrin-fed fish. A 50-fold molar excess of unlabeled DMBA reduced binding of 15 nmol [3H]DMBA/mg protein (nonspecific binding) by the same amount in cytosol from control and dieldrin-fed fish, indicating that dieldrin induced specific binding. Liver sections from control and dieldrin-fed fish were treated with multidrug resistance (MDR) protein monoclonal antibodies C494, C219, and JSB-1, and polyclonal antibody MDR Ab-1. There were no marked differences in optical densities of immunohistochemical staining near bile canaliculi of control and dieldrin-fed fish. Induction of xenobiotic binding capacity in cytosol of dieldrin-fed rainbow trout at least partially explained altered DMBA disposition in fish pretreated with this cyclodiene insecticide.
MDR1 基因特异性单克隆抗体 C494 与丙酮酸羧化酶发生交叉反应。
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狄氏剂预处理改变了虹鳟鱼肝脏切片中[14C]狄氏剂和[3H]7,12-二甲基苯并[a]蒽的摄取。
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