| First Author | Drake DM | Year | 2023 |
| Journal | Free Radic Biol Med | Volume | 208 |
| Pages | 272-284 | PubMed ID | 37541454 |
| Mgi Jnum | J:339667 | Mgi Id | MGI:7523769 |
| Doi | 10.1016/j.freeradbiomed.2023.08.006 | Citation | Drake DM, et al. (2023) Breast cancer 1 (BRCA1) protection in altered gene expression and neurodevelopmental disorders due to physiological and ethanol-enhanced reactive oxygen species formation. Free Radic Biol Med 208:272-284 |
| abstractText | The breast cancer 1 (Brca1) susceptibility gene regulates the repair of reactive oxygen species (ROS)-mediated DNA damage, which is implicated in neurodevelopmental disorders. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), including abnormal brain function, associated with enhanced ROS-initiated DNA damage. Herein, oxidative DNA damage in fetal brains and neurodevelopmental disorders were enhanced in saline-exposed +/- vs. +/+ Brca1 littermates. A single EtOH exposure during gestation further enhanced oxidative DNA damage, altered the expression of developmental/DNA damage response genes in fetal brains, and resulted in neurodevelopmental disorders, all of which were BRCA1-dependent. Pretreatment with the ROS inhibitor phenylbutylnitrone (PBN) blocked DNA damage and some neurodevelopmental disorders in both saline- and EtOH-exposed progeny, corroborating a ROS-dependent mechanism. Fetal BRCA1 protects against altered gene expression and neurodevelopmental disorders caused by both physiological and EtOH-enhanced levels of ROS formation. BRCA1 deficiencies may enhance the risk for FASD. |
