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Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
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Published on: May 29, 2019

Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits

Peter G Wells1, Gordon P McCallum, Kyla C H Lam

  • 1Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. pg.wells@utoronto.ca

Birth Defects Research. Part C, Embryo Today : Reviews
|June 15, 2010
PubMed

Insights

Teratogenic agents generate reactive oxygen species (ROS) causing oxidative DNA damage, impacting embryonic development primarily through altered gene transcription. Protective mechanisms exist but vary based on teratogen and developmental factors.

Area of Science:

  • Developmental toxicology
  • Molecular toxicology
  • Genetics

Background:

  • Teratogenic agents, including radiation and xenobiotics, induce reactive oxygen species (ROS).
  • ROS cause oxidative damage to cellular macromolecules like DNA, particularly 8-oxoguanine lesions.
  • This damage can adversely affect embryonic development, potentially via altered gene transcription.

Purpose of the Study:

  • To investigate the role of oxidative DNA damage in teratogenesis.
  • To explore the mechanisms by which ROS-initiating teratogens affect development.
  • To understand the protective roles of DNA repair and signaling pathways.

Main Methods:

  • Review of existing literature on teratogens, ROS, and DNA damage.
  • Analysis of mechanisms including gene transcription alterations, receptor-mediated processes, and adduct formation.
  • Examination of endogenous oxidative stress and its embryopathic consequences.
  • Evaluation of protective factors like p53, ATM, OGG1, and CSB.

Main Results:

  • Oxidative DNA damage, especially 8-oxoguanine, is a key mechanism in teratogenesis.
  • Altered gene transcription is a likely pathway, rather than direct mutation.
  • Other ROS effects and alternative mechanisms contribute to developmental toxicity.
  • Endogenous oxidative stress can cause developmental issues if detoxification/repair pathways are insufficient.

Conclusions:

  • Oxidative stress is a significant factor in teratogenesis, impacting embryonic development.
  • Developmental outcomes depend on the interplay between teratogen exposure, ROS production, and cellular defense mechanisms.
  • Protective pathways are crucial but their efficacy varies, highlighting the complexity of developmental toxicity.

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