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Main Title Diethyldithiocarbamate Potentiates the Neurotoxicity of In vivo 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine and of In vitro 1-Methyl-4-Phenylpyridinium.
Author Miller, D. B. ; Reinhard, J. F. ; Daniels, A. J. ; O'Callaghan, J. P. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. ;Wellcome Research Labs., Research Triangle Park, NC.
Publisher c1991
Year Published 1991
Report Number EPA/600/J-91/199;
Stock Number PB91-242586
Additional Subjects Toxicity ; Nervous system ; Diethyldithiocarbamate ; Adrenal medulla ; Glial fibrillary acidic protein ; Corpus striatum ; Dopamine ; Norepinephrine ; Tyrosine hydroxylase ; Catalepsy ; Cell survival ; Mice ; In vivo analysis ; Reprints ; Methylphenyl tetrahydropyridine ; Methylphenylpyridium
Library Call Number Additional Info Location Last
NTIS  PB91-242586 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 11p
Diethyldithiocarbamic acid (DDC), a dithiocarbamate, potentiates the neurotoxicity of 1-methyl-r-pheny-1,2,3,6-tetrahydropyridine (MPTP) in vivo and of its major metabolite, 1-methyl-4-phenylpyridinium (MPP+), in bovine adrenal medullary (BAM) cells maintained in culture. Male C57B1/6 mice were given 2 or 5 injections of MPTP (30mg/kg, i.p.) preceded 0.5 hy by DDC (400 mg/kg, i.p.). The mice were tested for catalepsy, akinesia or motor activity during and after the period of dosing. Systemically administered MPP+ decreased heart NE but did not alter the striatal levels of DA or GRAP & pretreatment with DDC did not alter these effects but did increase lethality. In culture MPP+ (0.3mM) slightly decreased catecholamine levels but had no effect on the tyrosine hydroxylase activity or cellular protein of BAM cells. However, the incubation of these cells with MPP+ and DDC (1.5 or 3.0mM) caused large decreases in all indicators of cell viability. DDC also blocked the uptake of MPP+ into the vesicles of BAM cells. Findings show that DDC increases the neurotoxicity of MPTP in both striatum and hippocampus. One possible explanation for the ability of DDC to potentiate the in vitro effect of MPP+ on BAM cells is that DDC may cause a redistribution of MPP+ at the subcellular level.