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Mechanisms and Biomarkers (WG 4) page 40
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Astorg (1997) indicated that β-carotene itself did not affect the expression of rat cytochrome
P450 or phase II enzymes, whereas canthaxanthin and an associated product of β-carotene
namely β-apo-8’-carotenal both induced the CYP1A gene in mice. Further work (Gradelet,
1996) revealed that expression of this gene was mediated by activity following the binding of
a ligand to a specific intracellular receptor designated AH. Although canthaxanthin and the
carotenal were involved in the gene expression they did not bind to the receptor. In a separate
study (Astorg, 1997) lycopene was demonstrated to protect against the initiation of
preneoplastic foci by diethylnitrosamine treated rats. Lycopene did not appear to act through
its antioxidant properties, but rather through its modulating effect on the liver enzyme
activating, cytochrome P-450 2E1. It is unclear whether the active component was lycopene
or one of its associated products.
The genotoxicity of nitrogen oxide has been shown to be inhibited by carotenoids in short
term tests. Supplementation with β-carotene resulted in a significant decrease in inducible
nitric oxide synthase in patients with nonatrophic gastritis (Mannick, 1996).
Research on the metabolic activities of both lycopene and β-carotene, suggest that the all trans
parent compounds do not exhibit any metabolic activity. However associated products such as
β-apo-8’-carotenal and 2,6-cyclolycopene-1,5-diols may prove to be metabolically active in
the promotion of GAP junctions and enhancement of protective enzymes such as cytochrome
P450.
Carotenoid interactions with free radicals
Lycopene as an antioxidant
In plants carotenoids play a role in helping to quench and prevent the formation of ROS,
especially singlet oxygen that is formed during photosynthesis. The importance of this
interaction in healthy animals is uncertain. However, singlet oxygen can be formed during the
process of lipid peroxidation, and it has also been suggested by Tatsuzawa (1999) that singlet
oxygen is also produced during the activation of neutrophils. This is thought to be due to the
interaction of hypochlorous acid and hydrogen peroxide. The hypochlorous acid is produced
following the activity of myeloperoxidase, which acts upon hydrogen peroxide. This ROS is
produced following the activation of neutrophil NADPH oxidase.
Singlet oxygen quenching by carotenoids occurs via physical or chemical mechanisms. The
efficiency of the physical quenching greatly exceeds that of the chemical quenching. The
former process relies on the transfer of excitation energy from singlet oxygen to the