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Folic acid protects SWV/Fnn embryo fibroblasts against arsenic toxicity
Y Ruan1, M H Peterson, E M Wauson
1Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 68198-6260, USA.
Abstract:
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.
Insights
Folic acid protects cells from arsenic toxicity by supporting methyl metabolism. While it mitigates acute arsenic poisoning, its effect on long-term growth inhibition is limited.
Area of Science:
- Environmental toxicology
- Cellular metabolism
- Nutritional biochemistry
Background:
- Arsenic toxicity is linked to disruptions in cellular methyl metabolism.
- Folic acid plays a crucial role in methyl metabolism pathways.
Purpose of the Study:
- To investigate if folic acid supplementation can protect against arsenic-induced cytotoxicity and growth inhibition.
- To elucidate the role of methyl metabolism in arsenic's toxic effects.
Main Methods:
- SWV/Fnn embryo fibroblasts were cultured with varying folic acid concentrations.
- Cells were treated with sodium arsenite or dimethylarsinic acid (DMA).
- Cytotoxicity and growth inhibition were assessed, with comparisons to ethanol and staurosporine treatments.
Main Results:
- Folic acid demonstrated dose-dependent protection against sodium arsenite and DMA cytotoxicity.
- Folic acid did not protect against ethanol or staurosporine toxicity, indicating specificity.
- Folic acid showed a modest, delayed effect on arsenic's growth inhibitory impact.
Conclusions:
- Folic acid mitigates acute arsenic cytotoxicity, supporting the role of methyl metabolism disruption.
- The findings suggest specific protective mechanisms of folic acid against arsenic-related cellular damage.
- Further research into methyl metabolism is warranted for understanding arsenic toxicity.