Acrylamide and glycidamide impair neurite outgrowth in differentiating N1E.115 neuroblastoma without disturbing rapid bidirectional transport of organelles observed by video microscopy.
The nature of the pathogenic insult in acrylamide neuropathy is unknown, but axonal transport disturbances are suspected. Using N1E.115 neuroblastoma in vitro, we examined acrylamide and related compounds in terms of general cytotoxicity, ability to block neurite outgrowth, and effects on neurite integrity and fast axonal transport. Acrylamide, glycidamide, and methylene-bis-acrylamide were weakly cytotoxic in a 51Cr-release assay, but only at > or = 10 mM (order of efficacy: methylene-bis-acrylamide > glycidamide > acrylamide). Neurite outgrowth by differentiating cells was inhibited at 100-fold lower concentrations, with similar EC50 values for all three toxicants, i.e., acrylamide, 70 +/- 15 microM; methylene-bis-acrylamide, 92 +/- 31 microM; glycidamide, 120 +/- 30 microM. Only glycidamide (1 mM) caused degeneration of established neurites within a period of 48 h. Video-enhanced contrast differential interference contrast microscopy was used to test the effect of acrylamide and glycidamide on organelle transport in the neurites. In exposures of < or = 48 h at 1 mM, neither toxicant altered bidirectional organelle flux, measured as organelles transported per minute per micrometer of neurite diameter. Anterograde and retrograde organelle speeds were also undisturbed. These results suggest that mechanisms other than direct inhibition of organellar motility are responsible for acrylamide's neurotoxicity in vivo.
Brat
D J
DJ
Mayo Clinic/Foundation, Department of Pharmacology, Rochester, MN 55905.
Brimijoin
S
S
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009447:Neuroblastoma; D015388:Organelles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014741:Video Recording
D000178:Acrylamides; D000577:Amides; D004852:Epoxy Compounds; D020106:Acrylamide; C071834:glycidamide; C021221:N,N'-methylenebisacrylamide; C034666:propionamide