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We show herein that TD in rabbit embryo culture produces relevant embryopathies, including decreases in head\/brain development by 28% and limb bud growth by 71% (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Two TD hydrolysis products, 2\u2010phthalimidoglutaramic acid (PGMA) and 2\u2010phthalimidoglutaric acid (PGA), were similarly embryopathic, attenuating otic vesicle (ear) and limb bud formation by up to 36 and 77%, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). TD, PGMA, and PGA all increased embryonic DNA oxidation measured as 8\u2010oxoguanine (8\u2010oxoG) by up to 2\u2010fold (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Co\u2010 or pretreatment with the PHS inhibitors eicosatetraynoic acid (ETYA) or acetylsalicylic acid (ASA), or the free\u2010radical spin trap phenylbutylnitrone (PBN), completely blocked embryonic 8\u2010oxoG formation and\/or embryopathies initiated by TD, PGMA, and PGA. This is the first demonstration of limb bud embryopathies initiated by TD, as well as its hydrolysis products, in a mammalian embryo culture model of a species susceptible to TD\n                      <jats:italic>in vivo<\/jats:italic>\n                      , indicating that all likely contribute to TD teratogenicity\n                      <jats:italic>in vivo<\/jats:italic>\n                      , in part through PHS\u2010dependent, ROS\u2010mediated mechanisms.\u2014Lee, C. J. J., Gon\u00e7alves, L. L., Wells, P. G. Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)\u2010dependent, reactive oxygen species (ROS)\u2010mediated mechanism.\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 2468\u20132483 (2011).\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1096\/fj.10-178814","type":"journal-article","created":{"date-parts":[[2011,4,18]],"date-time":"2011-04-18T23:40:22Z","timestamp":1303170022000},"page":"2468-2483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)\u2010dependent, reactive oxygen species (ROS)\u2010mediated mechanism"],"prefix":"10.1096","volume":"25","author":[{"given":"Crystal J. 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