Gilroy D J, Miranda C L, Siddens L K, Zhang Q, Buhler D R, Curtis L R
Oak Creek Laboratory of Biology, Toxicology Program, Oregon State University, Corvallis 97331, USA.
Fundam Appl Toxicol. 1996 Apr;30(2):187-93. doi: 10.1006/faat.1996.0055.
We previously demonstrated that pretreatment of rainbow trout with the organochlorine insecticide dieldrin altered in vivo disposition of a subsequent [14C]dieldrin dose. This was not explained by changes in total lipid content or the activity of common xenobiotic metabolizing enzymes. We hypothesized that dieldrin induced hepatic proteins responsible for organochlorine (OC) sequestration, transport, or excretion and that these changes reflected an adaptive response of trout to OC exposure. Here, uptake of 1.18 microM [14C]-dieldrin by precision cut liver slices was increased by dieldrin pretreatment of rainbow trout. Uptake of 0.118 and 1.18 microM [3H]-7,12-dimethylbenz[a]anthracene (DMBA) and efflux of 0.118 microM [3H]DMBA were significantly increased in slices from dieldrin-pretreated trout. Liver slice uptake of 10 but not 1.18 microM [3H]-estradiol and [3H]cholic acid was significantly increased by dieldrin pretreatment. There were no such significant differences for [3H]cholesterol, [3H]cholesterol-oleate, or [3H]oleic acid uptake. Dieldrin pretreatment did not alter hepatic microsomal metabolism of [3H]DMBA or [14C]benzo[a]pyrene or content of six cytochrome P450 isozymes, as quantitated by Western Blot analysis. These results provide further evidence that altered disposition of [14C]dieldrin and [3H]DMBA in dieldrin-pretreated trout was not explained by microsomal enzyme induction but reflected altered processes integral to hepatocellular transmembrane kinetics. These changes may have important implications for OC bioaccumulation by rainbow trout and demonstrate an interaction between dieldrin and DMBA in the absence of cytochrome P450 system induction.
我们之前证明，用有机氯杀虫剂狄氏剂对虹鳟鱼进行预处理会改变后续[14C]狄氏剂剂量在体内的处置情况。这不能用总脂质含量或常见外源性物质代谢酶活性的变化来解释。我们推测狄氏剂诱导了负责有机氯（OC）螯合、转运或排泄的肝蛋白，并且这些变化反映了鳟鱼对OC暴露的适应性反应。在此，经狄氏剂预处理的虹鳟鱼的精确切割肝切片对1.18微摩尔[14C] - 狄氏剂的摄取增加。在经狄氏剂预处理的鳟鱼的切片中，0.118和1.18微摩尔[3H] - 7,12 - 二甲基苯并[a]蒽（DMBA）的摄取以及0.118微摩尔[3H]DMBA的流出均显著增加。狄氏剂预处理使肝切片对10微摩尔而非1.18微摩尔[3H] - 雌二醇和[3H]胆酸的摄取显著增加。对于[3H]胆固醇、[3H]胆固醇油酸酯或[3H]油酸的摄取，没有此类显著差异。狄氏剂预处理未改变[3H]DMBA或[14C]苯并[a]芘的肝微粒体代谢，也未改变通过蛋白质免疫印迹分析定量的六种细胞色素P450同工酶的含量。这些结果提供了进一步的证据，表明在经狄氏剂预处理的鳟鱼中，[14C]狄氏剂和[3H]DMBA处置的改变并非由微粒体酶诱导所致，而是反映了肝细胞跨膜动力学所固有的过程改变。这些变化可能对虹鳟鱼体内OC的生物累积具有重要意义，并证明在不存在细胞色素P450系统诱导的情况下狄氏剂与DMBA之间存在相互作用。
