NDLI: Cytotoxicity of organophosphate anticholinesterases

Content Provider	Springer Nature Link
Author	Cao, C. J. Mioduszewski, R. J. Menking, D. E. Valdes, J. J. Katz, E. J. Eldefrawi, M. E. Eldefrawi, A. T.
Copyright Year	1999
Abstract	Organophosphate (OP) anticholinesterases were found to modulate metabolic activities of human neuroblastoma cells and hepatocytes, which was detectable by the Cytosensor® microphysiometer. The nerve gas ethyl-S-2-diisopropylaminoethyl methylphosphorothiolate (VX), at 10 µM, produced significant reduction in cell metabolism within 2 min, as measured by changes in the acidification rate of the medium. The reduction was dose-and time-dependent and irreversible after 4 h of exposure. Two alkaline degradation products of VX produced no cytotoxicity. Exposure for 24 h to 3 µM VX caused 36% and 94% irreversible loss of metabolism in hepatocytes and neuroblastoma cells, respectively. The insecticides parathion and chlorpyrifos stimulated hepatocyte metabolism but inhibited neuroblastoma cells. Their oxons were more active. Exposure of neuroblastoma cells for 4 h to VX, parathion, paraoxon, diisopropylfluorophosphate or chlorpyrifos gave an LC$_{50}$ of 65, 775, 640, 340, or 672 µM, respectively, whereas 24 h gave an LC$_{50}$ of 0.7, 3.7, 2.5, 29, and 31 µM, respectively. Preincubation of hepatocytes with phenobarbital enhanced their response to parathion and VX due to metabolic bioactivation. Atropine partially blocked the effects of VX and paraoxon on both cell types, which suggests the involvement of a muscarinic receptor as the target for cytotoxicity. There was no correlation between OP in vivo neurotoxicity and in vitro cytotoxicity. It is suggested that the former results from their cholinesterase inhibition, while the latter results from action on different targets and requires much higher concentrations.
Starting Page	493
Ending Page	500
Page Count	8
File Format	PDF
ISSN	10712690
Journal	In Vitro Cellular & Developmental Biology - Animal
Volume Number	35
Issue Number	9
e-ISSN	1543706X
Language	English
Publisher	Springer-Verlag
Publisher Date	1999-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	bioactivation enzyme induction hepatocytes human cell cultures in vitro cytotoxicity media acidification rate microphysiometer neuroblastoma cells organophosphate anticholinesterases Cell Biology Developmental Biology Animal Genetics and Genomics Animal Biochemistry Animal Physiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine

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