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Mechanisms and Biomarkers (WG 4) page 64
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council against the search for that elusive ‘magic bullet’ lest we shoot ourselves in the foot
(again)!
Proposals for future research
Health-related studies
Experimental design.
1. The use of food-derived, synergistic mixtures of AO/protective components, delivered to
the appropriate animal or cell systems at physiologically relevant concentrations.
2. Establishment of base-line AO levels to avoid using AO-replete test systems.
3. More use of primate and pig model systems to simulate human studies.
4. Nothing less than a revolution is required in the field of cell culture where we currently use
transformed cell lines to study the role of AO in cancer prevention.
It is a major priority in this field of research to switch to stem cell lines or SV40-immortalised
cell lines if we are to study the effects of AO and oxidants on ‘normal’ rather than mutated
cell lines.
5. If we are to determine the true AO or prooxidant properties of dietary components in cell
culture systems , then the appropriate O2 tension must be employed ie. 10-20ppm for body
tissues vs 160mm atmospheric.
6. To move away from the simple chemical degradation products as biomarkers of protein and
DNA damage to analyse macromolecular damage and gene-products induced by oxidant
stress or AO protection.
7. To assess the role of population genetics in response to oxidative stress and dietary
intervention. Recent advances in molecular biology will allow the rapid and simultaneous
analysis of thousands of expressed genes using oligonucleotide arrays.
The advantage of this approach is two-fold. It will give an unequivocal response of healthy
subjects to oxidative stress/AO protection in terms of gene expression , but will also reveal
subjects with gene defects that place them at increased risk from oxidative stress eg. those
with haemochromatosis, glutathione deficiency, methylene tetrahydrofolate reductase
mutations etc for whom appropriate dietary strategies can be designed and prescribed.
Plant Production and Quality Control
The message from WG4 which is supported by much recent AO research, is that a tomato
(product) with a balanced array of protective AO components is preferable to an engineered