Deficient DNA repair exacerbates ethanol-initiated DNA oxidation and embryopathies in ogg1 knockout mice: gender risk and protection by a free radical spin trapping agent

Miller-Pinsler, Lutfiya; Wells, Peter G.

doi:10.1007/s00204-014-1397-1

Cited by 19 publications

(30 citation statements)

References 33 publications

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“…The presence of neurodevelopmental abnormalities in untreated OGG1‐deficient mice has been corroborated by another group (Bjørge et al, ). Similarly, OGG1‐deficient progeny exhibited more severe, sex‐dependent embryopathies when exposed to EtOH in whole embryo culture (Miller‐Pinsler & Wells, ), compared to EtOH‐exposed +/+ littermates, which were also protected by PBN pretreatment, providing the most direct evidence to date that oxidatively damaged DNA, as distinct from altered ROS‐mediated signal transduction, may play a pathogenic role in FASD. Although the role of OGG1 in neurodevelopmental abnormalities in humans is currently not known, various OGG1 polymorphisms (Figure ), in particular Ser326Cys, have been associated with an increase in risk for a variety of cancers (Ali, Mahjabeen, Sabir, Mehmood, & Kayani, ; Peng et al, ; Zhou, Li, Ji, Wang, & Gao, ), with respective reductions in OGG1 activity of 14% in heterozygous (Ser/Cys) and 20% in homozygous (Cys/Cys) subjects (Simonelli et al, ; Weiss, Goode, Ladiges, & Ulrich, ), and a further decrease in activity in vitro under oxidizing conditions (Kershaw & Hodges, ; Lee, Hodges, & Chipman, ; Simonelli et al, ).…”

Section: Dna Repairmentioning

confidence: 99%

“…However, even physiological levels of ROS can be harmful in genetically or environmentally predisposed progeny, as they can cause altered signal transduction and/or oxidative macromolecular damage, including DNA damage and altered gene expression, which may contribute to teratogenesis (Figure ). For example, ROS‐initiated birth defects and postnatal neurodevelopmental abnormalities occur in untreated mutant or knockout (KO) mice with: (a) deficient ROS detoxification (glucose‐6‐phosphate dehydrogenase (G6PD; Nicol, Zielenski, Tsui, & Wells, ; Wells, Bhatia, Drake, & Miller‐Pinsler, ) or catalase (Abramov, Tran, Shapiro, & Wells, ; Abramov & Wells, ; Abramov & Wells, )); or (b) deficient DNA repair (oxoguanine glycosylase 1 (OGG1; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ) or breast cancer 1 protein (BRCA1; Shapiro et al, )]. However, ROS levels in the fetus can also be enhanced by in utero exposure to environmental chemicals or drugs, resulting in oxidative stress.…”

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

“…However, ROS levels in the fetus can also be enhanced by in utero exposure to environmental chemicals or drugs, resulting in oxidative stress. This has especially been implicated in the developmental toxicity of ethanol (EtOH; Dong, Sulik, & Chen, ; Miller, Shapiro, & Wells, ; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ; Tables , Figure ) and several other drugs including methamphetamine (Cadet & Krasnova, ; Jeng, Wong, Ting‐A‐Kee, & Wells, ; Wong, McCallum, & Wells, ), phenytoin (Abramov et al, ; Abramov & Wells, ; Winn & Wells, ), and thalidomide (Hansen & Harris, ; Lee, Goncalves, & Wells, ; Parman, Wiley, & Wells, ; Knobloch, Schmitz, Götz, Schulze‐Osthoff, & Rüther, ), for which animal models reflect human developmental outcomes (Figures and ).…”

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

“…However, the extent of ROS‐mediated direct alterations in developmental signal transduction pathways versus oxidative damage to embryonic and fetal cellular macromolecules like DNA is not known. Here, we discuss the evidence supporting the role of oxidative damage to macromolecules such as DNA, as a pathogenic mechanism involved in EtOH‐initiated embryopathies and neurodevelopmental abnormalities, which is evident at minimally developmentally toxic doses and concentrations of EtOH in various animal models via epigenetic and nonepigenetic mechanisms (Basavarajappa & Subbanna, ; Brooks, ; Galligan et al, ; Haycock, ; Mandal, Halder, Jung, & Chai, ; Miller‐Pinsler et al, ; Miller‐Pinsler & Wells, ; Shapiro et al, ; Shapiro, Miller, & Wells, , Ungerer et al, ; Varadinova & Boyadjieva, ; Tables , Figures & ). For example, a single administration of EtOH to gestational Day 17 pregnant dams increases the level of oxidatively damaged DNA (i.e., 8‐oxoG) in fetal brains of −/− Ogg1 mice lacking OGG1 (the major enzyme that repairs the 8‐oxoG lesion; Miller, Shapiro, Cheng, & Wells, ).…”

Section: Involvement Of Ros‐mediated Macromolecular Damage Versus Sigmentioning

confidence: 99%

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Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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This review covers molecular mechanisms involving oxidative stress and DNA damage that may contribute to morphological and functional developmental disorders in animal models resulting from exposure to alcohol (ethanol, EtOH) in utero or in embryo culture. Components covered include: (a) a brief overview of EtOH metabolism and embryopathic mechanisms other than oxidative stress; (b) mechanisms within the embryo and fetal brain by which EtOH increases the formation of reactive oxygen species (ROS); (c) critical embryonic/fetal antioxidative enzymes and substrates that detoxify ROS; (d) mechanisms by which ROS can alter development, including ROS-mediated signal transduction and oxidative DNA damage, the latter of which leads to pathogenic genetic (mutations) and epigenetic changes; (e) pathways of DNA repair that mitigate the pathogenic effects of DNA damage; (f) related indirect mechanisms by which EtOH enhances risk, for example by enhancing the degradation of some DNA repair proteins; and, (g) embryonic/fetal pathways like NRF2 that regulate the levels of many of the above components. Particular attention is paid to studies in which chemical and/or genetic manipulation of the above mechanisms has been shown to alter the ability of EtOH to adversely affect development. Alterations in the above components are also discussed in terms of: (a) individual embryonic and fetal determinants of risk and (b) potential risk biomarkers and mitigating strategies. FASD risk is likely increased in progeny which/who are biochemically predisposed via genetic and/or environmental mechanisms, including enhanced pathways for ROS formation and/or deficient pathways for ROS detoxification or DNA repair.

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Section: Dna Repairmentioning

confidence: 99%

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

Section: The Relationship Between Reactive Oxygen Species Oxidative mentioning

confidence: 99%

Section: Involvement Of Ros‐mediated Macromolecular Damage Versus Sigmentioning

confidence: 99%

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Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Bhatia

Drake

Miller

et al. 2019

Birth Defects Research

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“…The explicit mechanisms of ROS‐initiated developmental toxicity are complex, but likely involve alterations in signal transduction (Hansen and Harris, ) and/or oxidative damage to cellular macromolecules like lipids, proteins, RNA, and DNA (Cooke et al, ; Wells et al, ), including the embryopathic DNA lesion 8‐oxoguanine (8‐oxoG) (Wong et al, ; Miller‐Pinsler et al, ; Miller‐Pinsler and Wells, ), which is repaired by oxoguanine glycosylase 1 (OGG1) (Wells et al, ) (Fig. ).…”

Section: Introduction and Background: Reactive Oxygen Species (Ros) mentioning

confidence: 99%

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine

Wells

Bhatia

Drake

et al. 2016

Birth Defects Research Pt C

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In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc.

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Mouse Whole Embryo Culture

Tung

Winn

2019

Methods in Molecular Biology

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Deficient DNA repair exacerbates ethanol-initiated DNA oxidation and embryopathies in ogg1 knockout mice: gender risk and protection by a free radical spin trapping agent

Cited by 19 publications

References 33 publications

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Oxidative stress and DNA damage in the mechanism of fetal alcohol spectrum disorders

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine

Mouse Whole Embryo Culture

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