Cao_1999_In.Vitro.Cell.Dev.Biol.Anim_35_493

Reference

Title : Cytotoxicity of organophosphate anticholinesterases - Cao_1999_In.Vitro.Cell.Dev.Biol.Anim_35_493
Author(s) : Cao CJ , Mioduszewski RJ , Menking DE , Valdes JJ , Katz EJ , Eldefrawi ME , Eldefrawi AT
Ref : In Vitro Cell Developmental Biology Anim , 35 :493 , 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 microM, 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 microM 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 LC50 of 65, 775, 640, 340, or 672 microM, respectively, whereas 24 h gave an LC50 of 0.7, 3.7, 2.5, 29, and 31 microM, 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.

PubMedSearch : Cao_1999_In.Vitro.Cell.Dev.Biol.Anim_35_493
PubMedID: 10548430

Related information

Inhibitor VX

Citations formats

Cao CJ, Mioduszewski RJ, Menking DE, Valdes JJ, Katz EJ, Eldefrawi ME, Eldefrawi AT (1999)
Cytotoxicity of organophosphate anticholinesterases
In Vitro Cell Developmental Biology Anim 35 :493

Cao CJ, Mioduszewski RJ, Menking DE, Valdes JJ, Katz EJ, Eldefrawi ME, Eldefrawi AT (1999)
In Vitro Cell Developmental Biology Anim 35 :493