Jun 15, 2010

Oxidative DNA damage and repair in teratogenesis and neurodevelopmental deficits

Birth Defects Research. Part C, Embryo Today : Reviews
Peter G WellsStephanie L Ondovcik

Abstract

Several teratogenic agents, including ionizing radiation and xenobiotics such as phenytoin, benzo[a]pyrene, thalidomide, and methamphetamine, can initiate the formation of reactive oxygen species (ROS) that oxidatively damage cellular macromolecules including DNA. Oxidative DNA damage, and particularly the most prevalent 8-oxoguanine lesion, may adversely affect development, likely via alterations in gene transcription rather than via a mutational mechanism. Contributions from oxidative DNA damage do not exclude roles for alternative mechanisms of initiation like receptor-mediated processes or the formation of covalent xenobiotic-macromolecular adducts, damage to other macromolecular targets like proteins and lipids, and other effects of ROS like altered signal transduction. Even in the absence of teratogen exposure, endogenous developmental oxidative stress can have embryopathic consequences in the absence of key pathways for detoxifying ROS or repairing DNA damage. Critical proteins in pathways for DNA damage detection/repair signaling, like p53 and ataxia telangiectasia mutated, and DNA repair itself, like oxoguanine glycosylase 1 and Cockayne syndrome B, can often, but not always, protect the embryo from ROS-initiating tera...Continue Reading

  • References17
  • Citations34

References

Mentioned in this Paper

Guanine
Embryo
Biochemical Pathway
Covalent Interaction
Cockayne Syndrome
Embryopathies
DNA Repair
Entire Embryo
Transcription, Genetic
Base Excision Repair

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