Evaluation of the spinal cord neuron X neuroblastoma hybrid cell line NSC-34 as a model for neurotoxicity testing.
NSC-34 is a hybrid cell line produced by fusion of motor neuron enriched, embryonic mouse spinal cord cells with mouse neuroblastoma. Cultures contain two populations of cells: small, undifferentiated cells that have the capacity to undergo cell division and larger, multi-nucleate cells that express many properties of motor neurons. The utility of NSC-34 cells as a model for investigation of neurotoxicity was evaluated following exposure of cultures to a selection of chemicals known to be neurotoxic to motor neurons. NSC-34 responded to agents that affect voltage-gated ion channels, cytoskeletal organization and axonal transport. The sensitivity of action potential production to various ion channel blockers was similar to that in primary motor neurons in culture. 2,5-hexanedione induced focal aggregation of neurofilaments in perikarya 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 electrophysiological evidence of synaptic connections between NSC-34 cells was obtained. Exposure to 1 mM glutamate had no effect on cell morphology or action potential production. Difficulties in using this line to investigate chemical neurotoxicity were poor substrate adhesion, requirement for routine subculture and change in expression of the neuronal phenotype with repeated subculture.
Durham
H D
HD
Montreal Neurological Institute, McGill University, Quebec, Canada.
Dahrouge
S
S
Cashman
N R
NR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D003470:Culture Media; D005069:Evaluation Studies as Topic; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006588:Hexanones / Q000494:pharmacology; D006822:Hybrid Cells / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013120:Spinal Cord Neoplasms / Q000473:pathology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013871:Thiones
D003470:Culture Media; D005971:Glutamates; D006588:Hexanones; D018377:Neurotransmitter Agents; D011725:Pyridines; D013871:Thiones; D018698:Glutamic Acid; D013779:Tetrodotoxin; C008704:pyrithione; C011269:2,5-hexanedione