Numerous approaches have been studied to degrade organophosphorus (OP) compounds and ameliorate their toxicity. In the current study, the potential of genetically engineered
organophosphorus hydrolase (OPH)
enzymes to functionally biotransform OP neurotoxicants was examined by assessing effects of OPH-hydrolyzed OPs on acute and delayed indicators of neurotoxicity. SY5Y human
neuroblastoma cells were used as a model test system, as these cells respond distinctly to
mipafox, which produces OP-induced delayed neuropathy, and
paraoxon, which does not. Short-term effects of four OPH-treated OPs on
acetylcholinesterase (AChE) and
neuropathy target esterase (NTE) activities were measured in
retinoic acid-differentiated or undifferentiated cells, and delayed effects of OPH-treated
paraoxon or
mipafox on levels of neuronal
cytoskeletal proteins in
nerve growth factor (
NGF)-differentiated cells. The anti-AChE activity of
paraoxon (maximum 3 muM) and anti-NTE activity of
mipafox (250 muM) in SY5Y cells were prevented by biodegradation with OPH. Anti-AChE activities of
mipafox,
methyl parathion, and
demeton-S were partially ameliorated, depending on OP concentration. Intracellular amounts of the 200-kD
neurofilament protein NF200 were unchanged
after treatment with OPH-treated or
buffer-treated
paraoxon, as expected, as this endpoint is insensitive to
paraoxon. However, NF200 levels rose in cells treated during late differentiation with OPH-treated
mipafox. This finding suggests the existence of a threshold concentration of
mipafox below which SY5Y cells can maintain their viability for compensating cellular damage due to
mipafox in neurite elongation. These results indicate that OPH may be used to biodegrade OPs and remediate their neurotoxic effects in vitro and that AChE and NTE are suitable detectors for OPH amelioration.