| First Author | Miller-Pinsler L | Year | 2015 |
| Journal | Free Radic Biol Med | Volume | 78 |
| Pages | 23-9 | PubMed ID | 25311828 |
| Mgi Jnum | J:220197 | Mgi Id | MGI:5632452 |
| Doi | 10.1016/j.freeradbiomed.2014.09.026 | Citation | Miller-Pinsler L, et al. (2015) Oxidative DNA damage in the in utero initiation of postnatal neurodevelopmental deficits by normal fetal and ethanol-enhanced oxidative stress in oxoguanine glycosylase 1 knockout mice. Free Radic Biol Med 78:23-9 |
| abstractText | Studies in mice with deficient antioxidative enzymes have shown that physiological levels of reactive oxygen species (ROS) can adversely affect the developing embryo and fetus. Herein, DNA repair-deficient progeny of oxoguanine glycosylase 1 (ogg1)-knockout mice lacking repair of the oxidative DNA lesion 8-oxo-2'-deoxyguanosine (8-oxodGuo) exhibited enhanced postnatal neurodevelopmental deficits, revealing the pathogenic potential of 8-oxodGuo initiated by physiological ROS production in fetal brain and providing the first evidence of a pathological phenotype for ogg1-knockout mice. Moreover, when exposed in utero to ethanol (EtOH), ogg1-knockout progeny exhibited higher levels of 8-oxodGuo in fetal brain and more severe postnatal neurodevelopmental deficits than wild-type littermates, both of which were blocked by pretreatment with the free radical trapping agent phenylbutylnitrone. These results suggest that ROS-initiated DNA oxidation, as distinct from altered signal transduction, contributes to neurodevelopmental deficits caused by in utero EtOH exposure, and fetal DNA repair is a determinant of risk. |
