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Application of protein profiles to identify common mechanism groups of pyrethrins and pyrethroids
Project Code: T10020
Section of Experimental Medicine and Toxicology, Imperial College London
Boobis, A ; Edwards, R
In its report on Risk Assessment of Mixtures of Pesticides and Similar Substances, the Committee on Toxicity of Chemicals in Food Consumer Products and the Environment (COT) recommended that groups of pesticides having common targets of toxicological action should be identified. The Science Group of the Food Standards Agency prioritised five classes of pesticides/veterinary medicines to be assessed for common mechanism grouping including pyrethroids and natural pyrethrins. Pyrethrins and pyrethroids are acutely neurotoxic by interacting with Na+ channels. Other cellular targets, such as voltage-activated Ca2+ channels, may also be affected. Hence, to define common mechanism groups (CMGs) it is proposed to use intracellular protein profiles, determined by techniques such as surface-enhanced laser desorption/ionisation – time of flight (SELDI-TOF) mass spectrometry, in neuronally-derived cells such as SH-SY5Y. Effects on functional endpoints, such as neurotransmitter transport, would also be assessed. Proteins with changes suggestive of a CMG (e.g. common to structural analogues), would be identified by proteomics using liquid chromatography-tandem mass spectrometryand assessed for biological relevance from the pathways involved. The role of selected proteins in the functional responses of cells would be confirmed by blocking expression using small interference RNA species. The ultimate aim of the project was to identify a small number of functionally important proteins characteristic of each CMG, the number of protein profiles determining the number of CMGs.
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