| Abstrakt: |
The growing threat of international terrorism brings with it new scenarios for disaster. For example, in the case of toxic organophosphorus compounds (OPs), it possible for terrorists to use known agents or inadvertently to produce highly toxic OPs of unknown structure as the result of attacks on chemical plants or stockpiles of pesticides and other chemicals. Defending against such agents requires rapid, sensitive, and specific detection of them and their biological effects. Thus, the development of biomarkers of human exposures to OPs is a vital component of the system of prediction and early diagnosis of induced diseases. The phosphylating properties of OPs lead to their differential interactions with various serine esterases. These enzymes include primary targets, e.g., acetylcholinesterase (AChE, acute toxicity) and neuropathy target esterase (NTE, delayed neuropathy, OPIDN); as well as secondary targets, e.g., butyrylcholinesterase (BChE) and carboxylesterase (CaE), which act as scavengers of OPs. The set of activities of these esterases as well as that of paraoxonase (PON1), which can hydrolyze and detoxify OPs, constitutes the ˵esterase status″ of an organism that largely determines indi-vidual sensitivity to OPs and that may be used as a complex biomarker of exposure. This complex biomarker is more effective and informative than the standard determination of erythrocyte AChE and total blood cholinesterases. In particular, it assists with distinguishing between acute and delayed neurotoxicity induced by OPs, as we showed in experiments on acute exposure of hens to a neuropathic compound, O,O-dipropyl-O-dichlorovinyl phosphate. In addition, measuring decreased activities of BChE and CaE, which are often more sensitive biomarkers of OP exposure, allows us to reveal exposure to low doses, as demonstrated by treating mice with low doses of phosphorylated oximes. The aim of the ISTC Project summarized here is to develop a smart biosensor system for simultaneous analysis of a set of blood esterases including AChE, BChE, NTE, CaE, and PON1. The speed, sensitivity, and integrated approach of the method will allow hazards to be assessed and appropriate interventions to be recommended before overt toxic damage has occurred. [ABSTRACT FROM AUTHOR] |
