In vitro Studies of Neurotoxic Substances

摘要

An in vitro strategy for the evaluation of the neurotoxic potential of chemicals was developed. A number of investigations were undertaken to validate portions of the proposed test battery. The components of the test battery which were used are as follows: neuroblastoma cell lines and chick brain cell and organ culture tester cells; acetylcholinesterase, neuron-specific enolase, and neurotoxic esterase activity, and acetylcholine receptor number as neuronal end-points; acrylamides and organophosphates as model chemicals. The research also led to the developement of an in vitro alternative for the hen brain assay for neurotoxic esterase (which is predictive of delayed neuropathy), the validation of the use of phenyl 4-butyrate (which is commerically available) as a substitute substrate for phenyl valerate (which must be custom synthesized) in the neurotoxic esterase assay, and the development of an in vitro method for the evaluation of the efficacy of anti-organophosphate chemical defense agents, such as an anti-paraoxon monoclonal antibodies. Studies on acetylcholine receptors indicate that the receptor nubmer in chick brain cultures increases with time in culture as well as with exposure to organophosphates.