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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Cell damage through pentose phosphate pathway in fetus fibroblast cells exposed to methyl mercury
Jamileh Salar Amoli1, Abbas Barin, Mina Ebrahimi-Rad
1Department of Toxicology, Veterinary Faculty, Tehran University, Tehran, Iran.
Abstract:
Methylmercury (MeHg) is a global pollutant that causes malformations. There has been no direct evidence for the effect of MeHg on pentose phosphate pathway (PPP). In embryonic development, PPP is much more active. This pathway produces ribose for DNA/RNA production. It is possible that one of teratogenicity mechanisms of MeHg is through PPP. The fetus fibroblast cells were incubated with different concentrations of MeHg (0.1-100 μm). A dose-response dependence was observed in MTT assay. Transketolase activity and DNA content were determined in cell exposed to MeHg. A defect at the level of DNA content was observed. This amount of DNA was highly correlated with transketolase activity (r = 0.76). This study has demonstrated that the potential teratogenic action of MeHg is through PPP. To assess the protective effects of thiamin, the infected cells were incubated with different concentrations of thiamin. The obtained results show that thiamin pyrophosphate supplementation correlated with the toxicity. This finding confirms that thiamin therapy is suitable for the prevention of MeHg toxicity. Our study provides basic data for prevention and treatment of MeHg toxicity via boosting PPP.

