EVALUATION OF THE SPINAL-CORD NEURON X NEUROBLASTOMA HYBRID CELL-LINENSC-34 AS A MODEL FOR NEUROTOXICITY TESTING

NSC-34 is a hybrid cell line produced by fusion of motor neuron enrich ed, embryonic mouse spinal cord cells with mouse neuroblastoma. Cultur es contain two populations of cells: small, undifferentiated cells tha t have the capacity to undergo cell division and larger, multi-nucleat e cells that express many properties of motor neurons. The utility of NSC-34 cells as a model for investigation of neurotoxicity was evaluat ed following exposure of cultures to a selection of chemicals known to be neurotoxic to motor neurons. NSC-34 responded to agents that affec t voltage-gated ion channels, cytoskeletal organization and axonal tra nsport The sensitivity of action potential production to various ion c hannel blockers was similar to that in primary motor neurons in cultur e. 2,5-hexanedione induced focal aggregation of neurofilaments in peri karya and processes of NSC-34. Sodium pyridinethione induced swelling and retraction of processes. In contrast, NSC-34 was not a good model in which to investigate agents that affect synaptic transmission. No e lectrophysiological evidence of synaptic connections between NSC-34 ce lls was obtained. Exposure to 1 mM glutamate had no effect on cell mor phology or action potential production. Difficulties in using this lin e to investigate chemical neurotoxicity were poor substrate adhesion, requirement for routine subculture and change in expression of the neu ronal phenotype with repeated subculture. (C) 1993 Intox Press, Inc.