The presentation is entitled "Oxidatively Generated
Damage to DNA: Mechanistic Aspects and Formation in Cells".
The survey provides up to date insight into
major oxidative degradation pathways of nucleobases in both isolated and cellular DNA.
Let me start with a few general considerations on the generation of
oxidative processes and their chemical and biochemical implications.
Superoxide radical is usually produced endogenously
through the respiration burst and the metabolism of xenobiotics.
These poorly reactive species can be converted into
hydrogen peroxide either by spontaneous or enzymatic dismutation.
Hydrogen peroxide can migrate within the cells,
since also it is not very reactive,
and in the presence of metal transition,
it can be converted into the highly reactive hydroxyl radical.
Hydroxyl radical can be produced as
an indirect effect of hydrogen radiation, for example.
Hydrogen radiation also can ionize, substrates as well as type one photosensitizer.
Photosensitization for type two mechanism can lead to the generation of a singlet oxygen.
All these reactive species and processes can damage DNA,
leading to the formation of different classes of lesions such as modified bases,
a basic site, single and double strand breaks,
DNA-protein cross-link, and also aldehyde adducts to aminobase.
As immediate or delayed consequences,
this modification can lead to lethality,
mutagenesis, carcinogenesis, and also aging.