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• W2078220376 abstract "Abstract BACKGROUND: During organogenesis the embryo is highly sensitive to oxidative stress. We hypothesize that oxidative stress and activation of a redox‐sensitive transcription factor, activator protein‐1 (AP‐1), are early indicators of embryonic stress in response to a teratogenic insult. 5‐Bromo‐2′‐deoxyuridine (BrdU) was chosen as a model teratogen to test this hypothesis; BrdU is a thymidine analog that is incorporated into replicating DNA. METHODS: 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‐1 DNA binding activity (c‐Fos‐ and c‐Jun‐dependent 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‐acetylcysteine, a glutathione precursor, was coadministered with BrdU to further explore the relationship between teratogenicity and redox homeostasis. RESULTS: BrdU exposure produced a dose‐dependent 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‐Jun DNA binding activity in embryos was not affected, c‐Fos DNA binding activity was elevated significantly 3 hr after BrdU exposure. Coadministration of N‐acetylcysteine decreased the skeletal malformations and AP‐1 DNA binding activity induced by BrdU. CONCLUSIONS: BrdU exposure induced an embryonic stress response manifested as an increase in oxidative stress and AP‐1 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. © 2006 Wiley‐Liss, Inc." @default.
• W2078220376 created "2016-06-24" @default.
• W2078220376 creator A5064334381 @default.
• W2078220376 creator A5070027264 @default.
• W2078220376 date "2006-08-01" @default.
• W2078220376 modified "2023-10-13" @default.
• W2078220376 title "Exposure to 5-Bromo-2′-deoxyuridine induces oxidative stress and activator protein-1 DNA binding activity in the embryo" @default.
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• W2078220376 doi "https://doi.org/10.1002/bdra.20284" @default.
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