il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

lipid membranes, proteins and DNA will result in the disruption of normal physiological
processes in the cell causing a damage to cell structures and giving rise to necrosis or
apoptosis (Cadenas and Davies 2000; Floyd and Carney 1992; Starke et al. 1997).
Cellular membranes, due to their high PUFA content, are the main targets for the lipid
peroxidation process. Peroxidation of membrane lipids will result in the disruption of
membrane semi-permeability and membrane fluidity that will have deleterious effects on
the membrane signaling process and may result in the cell death (Eze 1992; Kaul et al.
1993). A large amount of evidence suggests that oxidative stress may also result in the
structural modification of a number of proteins which will affect a normal functioning of
the cell. Proteins that contain sulphydryl groups are found most susceptible for free
radical attack. (Brown 1999; Pearce et al. 2001).
Oxidative stress-induced damage to nucleic acid was first described by exploring
the mutagenic and carcinogenic effects of ionizing radiation on biological systems.
Ionizing radiation causes a direct damage to DNA by producing high levels of hydroxyl
radicals due to the homolysis of intracellular water molecules. The free radical producing
effects of radiation play a signifîcant role in the pathogenesis of several diseases and may
be involved in the process of aging (Wiseman and Halliwell i996). Mitochondrial DNA
is also found to be affected by oxidative stress. This is due to the proximity of
mitochondrial DNA to the different free radical generating systems such as the oxidative
phosphorylation process (Wiseman and Halliwell 1996). DNA repair errzymes are also
targeted by the free radicals. Oxidative modification of repair enzymes will result in the
increased incidence of DNA strand erïors, which will ultimately lead to the development
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