Results obtained in cell cultures or in animal studies have demonstrated significant inhibitory effects of a number of ingredients of fruits and vegetables on cancer cell growth. Amongst these food compounds are the antioxidative vitamins A1, C2 and E3, the carotenoids4, minerals, such as calcium5 and selenium6, dietary fibres7 and flavonoids8. However, human intervention trials investigating the effects of those compounds in colon cancer patients have been more or less disappointing9"11. Even more unexpected results were obtained in the CARET12 study and the ATBC study13. Both primary prevention trials were stopped because of a higher lung cancer incidence and mortality in smokers when supplemented with p-carotene. What can be learned from this, is that compounds that are effective growth inhibitors in cancer cells are not necessarily good chemopreventive agents in vivo, and vice versa. In particular antioxidants are generally regarded as effective chemopreventive agents since they are potent scavengers ofreactive oxygen species (ROS). ROS-mediated DNA damage contributes to spontaneous mutagenesis, and cells with impaired repair mechanisms and with low concentrations of protective compounds, including antioxidants, have elevated levels of spontaneous mutations, which might initiate cancer development14. On the other hand, ROS may be essential as activators of programmed cell death (apoptosis) to remove cells that have accumulated mutations. It was demonstrated recently that the depletion of antioxidants was able to inhibit tumour growth in a transgenic mouse brain tumour model15. Moreover, anti-apoptotic proteins that act as antioxidants, such as bcl-2, are usually up-regulated in cancer cells as a mechanism to escape apoptosis16'17, supporting the notion that a high level of antioxidants could be fatal in allowing transformed cells to resist the cell death signals. What is important to remember is that every compound displays a distinct dose-response relationship. It was shown for
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