NO - Besoin d'assistance

Mechanisms and Biomarkers (WG 4) page 20
__________________________________________________________________________________________
a 13% decrease of total cancer deaths and another trial showed no effect on oesophageal
cancer risk. ATBC (1994) trial in Finland on former smokers showed significant increase of
18% in lung cancer incidence. Finally, a trial in USA fails to show any effect on the
occurrence of new colorectal adenomas in patients with a history of past adenomas.
Antioxidants may thus protect the cell towards initiation processes and are not thought to
influence the development of cancer even though ß-carotene was shown to be of benefit in
oral leukoplasia, precursor of oral cancer. Beneficial effect of antioxidants may also be
derived from other mechanisms such as enhancing the immune function or increasing the gap
junctions recently shown for carotenoids.
The association between oxidative stress and cancer was also suggested through earlier
correlation between increased iron stores and increased cancer of all organs (Stevens et al.,
1988). Similarly, another prooxidant substance, peroxynitrite, was linked to the formation of
and progression of tumours. Peroxynitrite production was identified in human colon
adenomas and carcinoma development related to the induction of nitric oxide synthases
(Ambs et al., 1998). Another mechanism by which peroxynitrite may be involved in
carcinogenosis is via its inhibitory effect on the p53 gene playing an important role in the
cellular response to DNA damage (Ambs et al., 1997). Direct evidence of DNA oxidation and
cancer has been shown in animal model (Unemura et al., 1990) by administration of iron
chelated to nitrilotriacetate (Fe-NTA) which causes kidney tumours and yielded a significant
increase of 8-oxo-dG, the most abundant and easily measured product of DNA oxidation.
Atherosclerosis and oxidative stress
It is now recognised that low density lipoproteins (LDL) play a significant pathogenic role in
atherosclerosis, a chronic disease, at the origin of angina pectoris, myocardial infarction and
ischaemic stroke (Parthasarathy et al., 1998). Atherosclerosis is the principal cause of death in
Western countries (>40% of all death). The atherogenic effects of oxidised LDL derived from
the oxidised lipid components which are able to induce adhesion molecules from monocytes
at the surface of endothelial cell surface and to modulate the chemotactic processes, cell
proliferation and are at the origin of lipid-laden foam cells, a first step of development of the
atherosclerotic lesion (Parthasarathy et al., 1999). Involvement of oxidative stress in the
development of atherosclerosis has been illustrated by the use of antioxidants that inhibit
atherogenesis. This protective effect can be explained by 2 mechanisms: a specific action on
LDL particles (exerted by vitamin E and ubiquinone) and the action at the tissue and cell
levels resulting in an increased uptake of antioxidants by vascular cells and increased cellular
antioxidant status which may result in a decrease of reactive oxygen species and in turn less