Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses

Epidemiological studies have clearly demonstrated a link between dietary ca rotenoids and the reduced incidence of certain diseases, including some can cers. However recent intervention studies (e.g. ATBC, CARET and others) hav e shown that beta-carotene supplementation has little or no beneficial effe ct and may, in fact, increase the incidence of lung cancers in smokers. Thi s presents a serious dilemma for the scientific community - are carotenoids at high concentrations actually harmful in certain circumstances? Currently, a significant number of intervention studies are on-going throug hout the world involving carotenoids (of both natural and synthetic origin) . Our approach has been to study the ability of supplementary carotenoids i n protecting cells against oxidatively-induced DNA damage las measured by t he comet assay), and membrane integrity las measured by ethidium bromide up take). Both lycopene and beta-carotene only afforded protection against DNA damage (induced by xanthine/xanthine oxidase) at relatively low concentrat ions (1-3 mu M). These levels are comparable with those seen in the plasma of individuals who consume a carotenoid-rich diet. However, at higher conce ntrations (4-10 mu M), the ability to protect the cell against such oxidati ve damage was rapidly lost and, indeed, the presence of carotenoids may act ually serve to increase the extent of DNA damage. Similar data were obtaine d when protection against membrane damage was studied. This would suggest that supplementation with individual carotenoids to sign ificantly elevate blood and tissue levels is of little benefit and, may, in fact, be deleterious. This in vitro data presented maybe significant in th e light of recent intervention trials.