Folic acid protects SWV/Fnn embryo fibroblasts against arsenic toxicity.
It has been proposed that arsenic exerts its toxic effects, in part, by perturbing cellular methyl metabolism. Based on the hypothesis that folic acid treatment will attenuate the cytotoxic and growth inhibitory effects of arsenic, SWV/Fnn embryo fibroblasts were cultured in media supplemented with various concentrations of folic acid during treatment with sodium arsenite or dimethylarsinic acid (DMA). It was found that folic acid protects SWV/Fnn embryo fibroblasts from sodium arsenite and DMA cytotoxicity in a dose-dependent manner. In contrast, folic acid supplementation has no effect on toxicity resulting from treatment with ethanol or staurosporine, suggesting that folic acid is not generally protective against necrosis and apoptosis. Although folic acid protects against acute arsenic toxicity, this agent shows a modest and delayed ability to attenuate the growth inhibitory effect of arsenic on these cells. These results support a model in which perturbations of methyl metabolism contribute to the acute cytotoxicity of arsenic.
Ruan
Y
Y
Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 68198-6260, USA.
Peterson
M H
MH
Wauson
E M
EM
Waes
J G
JG
Finnell
R H
RH
Vorce
R L
RL
D000818:Animals; D001151:Arsenic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018053:Arsenites / Q000037:antagonists & inhibitors / Q000633:toxicity; D002101:Cacodylic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005492:Folic Acid / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D017670:Sodium Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D019311:Staurosporine / Q000633:toxicity
D018053:Arsenites; D002273:Carcinogens; D002492:Central Nervous System Depressants; D017670:Sodium Compounds; D000431:Ethanol; C017947:sodium arsenite; D005492:Folic Acid; D002101:Cacodylic Acid; D019311:Staurosporine; D001151:Arsenic