NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 34
__________________________________________________________________________________________
PUFAs in animal and human cell membranes, making ethane and pentane the biomarkers of
choice for measuring membrane lipid peroxidation. Numerous studies have been carried out
which demonstrated increased alkane exhalation as a result of diseases or disorders which
have oxidative stress in their aetiologies, and correlate with many dietary factors and
toxicological agents (de Zwart et al., 1999). Although this technique has been widely used
over the last decade, there are practical limitations to the methods used. There are significant
background levels of both pentane and isoprene in human breath. Pentane is accepted as a
measure of lipid peroxidation but the background source of isoprene is, as yet, unknown.
Also, because of the similar boiling points the 2 compounds are very difficult to separate
(Springfield and Levitt, 1994). However, a new GC method has been developed which can
resolve pentane and isoprene (Mendis et al., 1994). It is tempting to speculate on the origin of
isoprene and this author would like to suggest that dietary carotenoids might be the source
following radical attack and cleavage. If this were to be the case then we have a valuable new
biomarker with which to follow the fate of plasma/tissue carotenoids in response to oxidative
stress.
Biomarker of Oxidative of DNA Damage
Can we use variation in the steady-state levels of DNA damage as an intermediate measure of
potential cancer risk?
RS can attack most biological molecules, but with respect to cancer and ageing DNA is
proposed as the major target in the absence of adequate data on the oxidative damage to
proteins, which may, in the future be found to have a significant role in controlling the fidelity
of polymerases, repair enzymes and gene expression (Dean, 1998).
Several reactive oxygen species can attack DNA directly to create mutagenic oxidation
products (Halliwell, 1998). This may contribute significantly to age related development of
cancer, therefore, a decrease in such damage should decrease the risk of cancer development.
A note of caution, when considering mechanisms of protection is that one must consider that
an agent decreasing steady state levels of oxidative DNA damage in vivo may do so either by
decreasing the rate of oxidative DNA damage and/or by increasing the rates of repair of such
damage (Halliwell, 1999).
RS can cause the formation of DNA-protein crosslinks, damage to the sugar phosphate
backbone and many specific chemical modifications of the purine and pyrimidine bases.
Oxidative base modification can cause mutations, whereas oxidation of the sugar moieties
induces base release or DNA strand breaks which can be conveniently analysed in the Comet
assay (see later). During the repair process endonucleases and glycosylases excise