Pesticide metabolism in humans, including polymorphisms.

Abstract

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.