The Physiological and Pathological Roles of Oxidative Damage to DNA in Relation to Life Stage

  • Alberto Izzotti
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Oxidative damage to DNA (ODD) is a common phenomenon occurring during all life stages in all aerobic organisms. To evaluate the biological significance of ODD, we monitored 8-hydroxy-2′-deoxyguanosine, lipophilic bulky DNA-adduct formation, and the expression of oxidative-stress related genes in a variety of animal and human studies.

In mouse foetal liver, the low basal level of ODD was increased following transplacental exposure to cigarette smoke. The foetus counteracted ODD by increasing the expression of genes inhibiting cell replication and triggering apoptosis. Accordingly, smoke-induced ODD in the foetus results in growth retardation. During the foetus-newborn transition, the acquisition of independent respiratory function triggers the expression of genes involved in the detoxification of reactive oxygen species and removal of oxidized proteins, as demonstrated in mouse lung. The most abundant ODD accumulation during lifetime, contributing to ageing, was detected in mouse heart and brain.

In humans, ODD is consistently detectable in the aorta of atherosclerotic patients, being 4-fold higher in the inner than in the medium layer.

To substantiate the hypothesis that ODD is related to various chronic-degenerative diseases, we analysed 8-hydroxy-2′-deoxyguanosine in the trabecular meshwork, the epithelium regulating the intra-ocular pressure, of patients affected by primary open angle glaucoma, the main cause of irreversible blindness worldwide. There was a significant (p<0.001), 3.4-fold, increase in ODD in glaucoma patients as compared to unaffected controls. This situation leads to an increase of intra-ocular pressure resulting in optic nerve alterations and visual field defects.

Altogether, these data support the view that ODD is involved in a variety of physiological processes (e.g., birth and ageing) and pathological conditions (e.g., intrauterine growth retardation, atherosclerosis and glaucoma).


Cigarette Smoke Life Stage Trabecular Meshwork Intrauterine Growth Retardation Primary Open Angle Glaucoma 
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Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Alberto Izzotti
    • 1
  1. 1.Department of Health SciencesUniversity of GenoaGenoaItaly

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