Rose R L, Tang J, Choi J, Cao Y, Usmani A, Cherrington N, Hodgson E
Department of Environmental and Molecular Toxicology, Box 7633, Raleigh, NC, 27695, USA.
Scand J Work Environ Health. 2005;31 Suppl 1:156-63; discussion 119-22.
Recent epidemiologic studies involving Gulf War veterans or agricultural workers suggest that pesticide-pesticide or pesticide-drug interactions may be related to Gulf-War-related illnesses or elevated cancer risks, respectively. Metabolic interactions are one of many potential mechanisms requiring exploration in humans. The goal of the studies is to characterize important metabolic profiles of selected pesticides and examine potential interactions to characterize human risks associated with exposure. Pesticides examined using human liver microsomes and cytosolic fractions included chlorpyrifos, carbaryl and permethrin. The metabolic pathways involved include cytochrome P450 monooxygenases (CYP), esterases, and alcohol and aldehyde dehydrogenases. Specific isoforms and some polymorphic enzymes were characterized. Pesticide-pesticide interactions with metabolizing enzymes were demonstrated. Exposure of human hepatocytes to chlorpyrifos and permethrin demonstrated their potential to induce CYP isoforms using the bDNA (branched deoxyribonucleic acid) assay [used to monitor mRNA (messenger ribonucleic acid) levels]. These studies suggest that knowledge of human metabolic pathways will provide information that can aid the risk assessment process.
最近涉及海湾战争退伍军人或农业工人的流行病学研究表明，农药与农药之间或农药与药物之间的相互作用可能分别与海湾战争相关疾病或癌症风险升高有关。代谢相互作用是需要在人体中探索的众多潜在机制之一。这些研究的目的是确定所选农药的重要代谢特征，并检查潜在的相互作用，以确定与接触相关的人类风险。使用人肝微粒体和胞质部分检测的农药包括毒死蜱、西维因和氯菊酯。涉及的代谢途径包括细胞色素P450单加氧酶（CYP）、酯酶以及醇和醛脱氢酶。对特定同工型和一些多态性酶进行了表征。证明了农药与代谢酶之间的相互作用。使用bDNA（分支脱氧核糖核酸）检测法（用于监测信使核糖核酸mRNA水平），将人肝细胞暴露于毒死蜱和氯菊酯中，证明了它们诱导CYP同工型的潜力。这些研究表明，了解人类代谢途径将提供有助于风险评估过程的信息。
