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Diethylene glycol monomethyl ether,ethylene glycol monomethyl ether and the metabolite, 2-methoxyacetic acid affect in vitro chondrogenesis
Affiliation:1. University of Georgia, Department of Environmental Health Science, Athens, GA, United States;2. University of Georgia, Interdisciplinary Toxicology Program, Athens, GA, United States;1. National Institute of Materials Physics, Laboratory of Optical Processes in Nanostructured Materials, Physics, Bucharest, R077125, P.O. Box MG-7, Romania;2. Institut des Matériaux “Jean Rouxel” (UMR CNRS-Université de Nantes n°6502), 2 rue de la Houssinière, B.P. 32229, F-44322, Nantes, France;3. Department of Chemistry, University of Craiova, Calea Bucuresti, 107I, 200478, Craiova, Romania;1. Directorate General for Health and Food Safety, 11, rue E. Ruppert, L-2920 Luxembourg, Luxembourg;2. Federal Institute for Risk Assessment (BfR), Berlin, Germany;1. TBS Associates, 7500 Rainwater Road, Raleigh, NC 27615, USA;2. Toxicology Consulting Services, 26881 Wedgewood Dr, Bonita Springs, FL 34134, USA;1. The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA;2. Toxicology Consulting Services, 26881 Wedgewood Dr., Bonita Springs, FL 34134, USA;3. Exponent Inc., 1910 St. Andrews St., Midland, MI 48640, USA;1. Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US FDA, Jefferson, AR, United States;2. Toxicology Excellence for Risk Assessment, Cincinnati, OH, United States;3. Toxicology Consulting Services, Bonita Springs, FL, United States;4. Exponent, Midland, MI, United States
Abstract:Diethylene glycol monomethyl ether (DEGME), ethylene glycol monomethyl ether (EGME) and their common metabolite, methoxyacetic acid (MAA) have been associated with adverse reproductive effects. The objective of this research is to investigate the effects of DEGME, EGME and MAA on in vitro chondrogenesis and the mechanisms by which these effects occur. Micromass cultures were exposed to DEGME, EGME or MAA for 5 days and proteoglycan abundance and cell proliferation determined. Longer-term 9- and 14-day cultures were exposed to MAA and apoptosis analyzed. All three chemicals decreased proteoglycan abundance and cell proliferation at the highest dose tested (100 μL/mL). However, only MAA showed a dose-dependent effect for both parameters at 0.01, 10, and 100 μL/mL. Furthermore, micromass cultures show an increase in apoptotic cells which when treated with MAA suggest that cell death could result from induced apoptosis. These results suggest that effects of DEGME and EGME are the result of generalized toxicity, but their metabolite MAA induces mitochondrial-mediated apoptosis during in vitro chondrogenesis.
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