{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:32:40Z","timestamp":1790775160382,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T00:00:00Z","timestamp":1157414400000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>During organogenesis the embryo is highly sensitive to oxidative stress. We hypothesize that oxidative stress and activation of a redox\u2010sensitive transcription factor, activator protein\u20101 (AP\u20101), are early indicators of embryonic stress in response to a teratogenic insult. 5\u2010Bromo\u20102\u2032\u2010deoxyuridine (BrdU) was chosen as a model teratogen to test this hypothesis; BrdU is a thymidine analog that is incorporated into replicating DNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Timed pregnant CD1 mice were given vehicle or BrdU (400, 600, 800, or 1000 mg of BrdU\/kg of body weight) on gestation day 9 (GD 9). Oxidative stress, assessed as the ratio of glutathione disulfide (GSSG) to reduced glutathione (GSH), and AP\u20101 DNA binding activity (c\u2010Fos\u2010 and c\u2010Jun\u2010dependent DNA binding) were measured in the maternal livers and embryos 0.5, 3, and 6 hr after treatment. External and skeletal malformations were assessed on GD 18. N\u2010acetylcysteine, a glutathione precursor, was coadministered with BrdU to further explore the relationship between teratogenicity and redox homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>BrdU exposure produced a dose\u2010dependent increase in skeletal malformations, which included polydactyly, and delayed ossification of the sternebrae and vertebrae. Exposure to teratogenic doses of BrdU depleted GSH concentrations and increased oxidative stress, as assessed by the GSSG:GSH ratio, in both maternal livers and embryos. While c\u2010Jun DNA binding activity in embryos was not affected, c\u2010Fos DNA binding activity was elevated significantly 3 hr after BrdU exposure. Coadministration of N\u2010acetylcysteine decreased the skeletal malformations and AP\u20101 DNA binding activity induced by BrdU.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>BrdU exposure induced an embryonic stress response manifested as an increase in oxidative stress and AP\u20101 DNA binding activity; these data support the hypothesis that disturbances in redox homeostasis mediate the response of the conceptus to a teratogenic insult. Birth Defects Research (Part A), 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20284","type":"journal-article","created":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T22:53:04Z","timestamp":1157496784000},"page":"580-591","source":"Crossref","is-referenced-by-count":22,"title":["Exposure to 5\u2010Bromo\u20102\u2032\u2010deoxyuridine induces oxidative stress and activator protein\u20101 DNA binding activity in the embryo"],"prefix":"10.1002","volume":"76","author":[{"given":"Sukhdeep Kaur","family":"Sahambi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara 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