Diethylene glycol monomethyl ether, ethylene glycol monomethyl ether and the metabolite, 2-methoxyacetic acid affect in vitro chondrogenesis.
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 microL/mL). However, only MAA showed a dose-dependent effect for both parameters at 0.01, 10, and 100 microL/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.
Scofield
Emily Hanson
EH
University of Georgia, Department of Environmental Health Science, Athens, GA 30602-2102, USA.
Henderson
W Matthew
WM
Funk
Amy B
AB
Anderson
Gary L
GL
Smith
Mary Alice
MA
D000085:Acetates / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D020219:Chondrogenesis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005026:Ethylene Glycols / Q000378:metabolism / Q000633:toxicity*; D018878:Limb Buds / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D000085:Acetates; D005026:Ethylene Glycols; D011509:Proteoglycans; C048214:diethylene glycol monomethyl ether; D053148:Caspase 3; D053453:Caspase 9; C005219:methyl cellosolve; C013598:methoxyacetic acid