| Sources of organophosphorus (OP) chemicals in the environment include agricultural, urban, and industrial applications and stockpiles of chemical warfare agents throughout the world. These compounds are potent neurotoxic chemicals in humans and animals and have caused significant impact on the environment. Hence, the need for effective and rapid OP detoxification technologies is globally critical. To this end, native and genetically engineered bacteria expressing organophosphorus hydrolase (OPH) were cryoimmobilized in polyvinyl alcohol to form stable, porous biocatalysts capable of OP degradation. In these studies, the impact of both diffusion and reaction rates on biocatalyst efficiency was determined, and the relative impact of substrate diffusion associated with microbial uptake was demonstrated. This research also presents a complete mathematical model for the degradation of neurotoxic OPs by cryoimmobilised cells that express a modified OPH with enhanced catalytic capabilities against an analog of chemical warfare agent VX. The bioreactor model of this system provides an important tool to evaluate the difficulties and opportunities of its potential applications. The broad substrate specificity of OPH, its remarkable hydrolytic efficiency, and the ability to genetically engineer the enzyme for specific target OP neurotoxins provide a unique opportunity for OPH-based technologies to be used in the destruction of organophosphorus neurotoxins. The cryoimmobilization technology provides an effective vehicle to develop a cost-effective and efficient remediation technology. Finally, the process design for remediation of hazardous wastes should provide reliable information regarding the detoxification potential of the technology. These potentials must be realized with the use of suitable biomarkers that address the breadth of toxic effects the wastes and their degradation products may cause. However, the neurotoxicology related to organophosphorus-induced delayed neuropathy (OPIDN) in humans and animals is not well understood. Therefore, this investigation examined the effects of OP compounds and their hydrolytic products on the SY5Y human neuroblastoma cells to further characterize cellular targets of OP neurotoxicity and efficiencies of detoxification. Hence, cellular mechanistic responses to organophosphorus neurotoxins were probed and the differences between acute short-term and OP-induced delayed neuropathies were distinguished, thus providing new biomarkers for consideration in the development of accurate, meaningful toxicological profiles of OP remediation technologies. |
