Carpenter H M, Curtis L R
Oak Creek Laboratory of Biology, Department of Fisheries and Wildlife, Oregon State University, Corvallis 97331.
Drug Metab Dispos. 1989 Mar-Apr;17(2):131-8.
Lipophilic chlorinated hydrocarbons pose a potential health hazard to humans and animals and the toxicity of a number of these compounds has been well documented. Despite the low environmental concentrations of most of these chemicals, much of the research conducted to date has used maximally tolerated doses. Our research, conducted with low, apparently nontoxic, doses of the insecticide chlordecone (CD), showed that the administration of CD (5 mg/kg ip) to mice (C57BL/6N and DBA/2N strains) caused a time-dependent alteration in the pattern of distribution of a subsequently administered dose of [14C]CD. Livers of CD-pretreated animals contained less label than did those from controls and CD pretreatment increased amounts of label in kidney, lung, fat, and muscle. Changes did not appear to be due to an altered rate of metaboLism and analysis of total CD in tissues (unlabeled plus [14C]CD) indicated that these responses were not due to a simple redistribution phenomenon. We have termed this preexposure effect a pretreatment disposition response (PDR) and feel it may reflect an important cellular response to lipophilic compounds. CD-induced PDR is dose related, exhibits a threshold, and is saturable at a given level of induction. In addition, PDR exhibits some specificity, inasmuch as pretreating mice with CD (5 mg/kg) does not alter the distribution of subsequently administered [14C]dieldrin. The characteristics of threshold, saturability, and specificity are consistent with the premise that CD-induced PDR is a protein-mediated phenomenon.
亲脂性氯代烃对人类和动物构成潜在的健康危害，其中许多化合物的毒性已有充分记载。尽管这些化学物质在环境中的浓度很低，但迄今为止进行的许多研究都使用了最大耐受剂量。我们用低剂量、明显无毒的杀虫剂开蓬（CD）进行的研究表明，给小鼠（C57BL/6N和DBA/2N品系）腹腔注射CD（5毫克/千克）会导致随后给予的一剂[14C]CD的分布模式随时间发生改变。经CD预处理的动物肝脏中的放射性标记物比对照组少，而CD预处理会增加肾脏、肺、脂肪和肌肉中的放射性标记物含量。这些变化似乎不是由于代谢速率改变所致，对组织中总CD（未标记的加[14C]CD）的分析表明，这些反应不是由于简单的重新分布现象。我们将这种预先接触效应称为预处理处置反应（PDR），并认为它可能反映了细胞对亲脂性化合物的一种重要反应。CD诱导的PDR与剂量相关，有一个阈值，并且在给定的诱导水平下是可饱和的。此外，PDR表现出一定的特异性，因为用CD（5毫克/千克）预处理小鼠不会改变随后给予的[14C]狄氏剂的分布。阈值、可饱和性和特异性的特征与CD诱导的PDR是一种蛋白质介导现象的前提一致。
