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Assessment of a 42 metal salts chemical library in mouse embryonic stem cells
Nichols, H., M. BARRIER, S. C. JEFFAY, S. CHANDLER, S. SIMMONS, AND E. S. HUNTER. Assessment of a 42 metal salts chemical library in mouse embryonic stem cells. Presented at Teratology Society Annual Meeting, San Diego, CA, June 25 - 29, 2011.
The adherent cell differentiation and cytotoxicity (ACDC) technique was used to evaluate a library of 42 metal and metaloid salts.
The developmental effects of xenobiotics on differentiation can be profiled using mouse embryonic stem cells (mESCs). The adherent cell differentiation and cytotoxicity (ACDC) technique was used to evaluate a library of 42 metal and metaloid salts. Jl mESCs were allowed to proliferate and differentiate in the 10-day assay. Using an In-Cell Western™ technique, cell number was determined using Sapphire700™/DRAQ5TM stains and cardiomyocyte differentiation was determined using an antibody to alpha-myosin heavy chain. Culture medium salt concentrations of 0.1, 1.0, 10 and 100 uM were evaluated. The concentration that produced a 25% change from control (AC25) was calculated using GraphPad Prism. Li, K, Ca, B, S, Fe(II), and Zn salts did not affect cell number or differentiation of mESCs at the concentrations evaluated. Cd, As(III), Zr, Ba, Ce, Sn(IV), La, Ti produced effects on differentiation at concentrations less than those that produced cytotoxicity. Cr(IV), AgN03, Co, Cu(II), As(V), Ti, Sn(II), AI, Fe(III), and Cr(IlI) produced cytotoxicity at concentrations less than those affecting differentiation. As(III), As(V), Cd, AgN03, and Cr(VI) were the most potent, affecting cell number and/or differentiation at < 10uM. Arsenicals, Cr(VI) and Cd are developmental toxicants in vivo and dysmorphogenic in whole embryo culture. The effects of these salts in the ACDC assay will be compared to those on heat shock protein and oxidative stress cell reporter assays to correlate activation ofthe stress pathways to perturbations in mESCs. This abstract does not represent EPA policy.