Hydroxyurea exposure triggers tissue-specific activation of p38 mitogen-activated protein kinase signaling and the DNA damage response in organogenesis-stage mouse embryos

• Published in: Toxicological sciences Vol. 133; no. 2; pp. 298 - 308
• Main Authors: Banh, Serena, Hales, Barbara F
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.06.2013
• Subjects: Abnormalities, Drug-Induced; Animals; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cytoplasm - drug effects; Cytoplasm - metabolism; DNA - drug effects; DNA Damage; Dose-Response Relationship, Drug; Embryo Culture Techniques; Embryo, Mammalian - drug effects; Embryo, Mammalian - metabolism; Female; Hydroxyurea - toxicity; MAP Kinase Kinase 3 - metabolism; MAP Kinase Kinase 6 - metabolism; Mice; Mice, Inbred Strains; Necrosis - chemically induced; Nucleic Acid Synthesis Inhibitors - toxicity; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Pregnancy; Signal Transduction - physiology; MAP2K3; replication stress; MEK3/6; appendicular skeleton; cell death; γH2AX; hindlimb; oxidative stress

Hydroxyurea (HU) is commonly used to treat myeloproliferative diseases and sickle cell anemia. The administration of HU to gestation day 9 CD1 mice causes predominantly hindlimb, tail, and neural tube defects. HU induces oxidative stress and p38 mitogen-activated protein kinase (MAPK) signaling in e...