Neuroblastoma cell lines were used to examine the differential interspecies response (i.e., species selectivity) to
organophosphates (OPs). Baseline activities of the major target
esterases, i.e.,
cholinesterase,
carboxylesterase, and
neurotoxic esterase, were assayed in mouse and several human neural candidate cell lines. These activities were found to be variable within individual cell lines and among the various tested cell lines. Cytotoxicity data using the
neutral red fluorometric assay were collected on both human (SH-SY5Y) and mouse (NB41A3)
neuroblastoma clones exposed to a variety of OP
insecticides. IC50 data indicated that the tested mouse cell line was consistently more sensitive than the human cell line to equimolar doses of various OP compounds (e.g.,
mipafox,
parathion,
paraoxon,
DFP,
leptophos oxon,
fenthion, and
fenitrothion). This difference in cytotoxic sensitivity was most pronounced in response to compounds requiring metabolic bioactivation (i.e., protoxicants). Cytotoxicity data also demonstrated that the NB41A3 mouse
neuroblastoma cell line was more metabolically competent than the SH-SY5Y human cell line in converting the protoxicant
parathion to its neurotoxic metabolite,
paraoxon. B-lymphoblastoids, genetically engineered with human P450 cDNAs, demonstrated higher cytotoxic sensitivity to
parathion than unengineered cells, indicating that
cytochrome P450-associated monooxidase activity could also influence cytotoxic sensitivity to
parathion in culture. These data suggest that interspecies-selectivity in response to OP-related cytotoxicity is influenced by intercellular differences in metabolism and baseline
esterase activities.