Reply to A Papas and E Vos

Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, E-mail: steven_zeisel{at}unc.edu

Dear Sir:

The point of my paper was that it is not always true that antioxidants help to prevent or eliminate cancers (1). There is no question that many studies report an association between increased consumption of antioxidants and decreased incidence of cancer, as noted by Papas and Vos. However, a growing body of evidence suggests that reactive oxygen species may not only regulate apoptotic signal transduction (2), but also actually activate apoptotic death pathways (3, 4). These pathways are extremely important for the elimination of cancer cells. Small increases in the concentration of reactive oxygen species within cells can induce apoptosis (3, 5). Exogenous prooxidants also can induce apoptosis (4, 6). Antioxidants such as -tocopherol, which is partitioned into the lipid compartment of cells, or N-acetylcysteine, a free radical scavenger that is partitioned into the aqueous phase of the cytosol, can delay or inhibit apoptosis (7, 8). We recently reported the result of a study in which TgT121 p53+/p53- transgenic mice, which spontaneously develop brain tumors in the choroid plexus, were fed a modified rodent diet devoid of antioxidant vitamins A and E, a control diet, or an antioxidant-supplemented diet (9). In the brain tumors of the antioxidant-depleted animals, overgeneration of reactive oxygen species and DNA oxidative impairment were detected by an increase in 8-oxoguanine residues. Depletion of antioxidants led to a rise in apoptosis in brain tumors, but not in normal tissues (brain, liver, spleen, intestine); this led to a significant reduction in tumor size. In contrast, feeding an antioxidant-rich diet neither increased apoptosis nor reduced tumor growth or total tumor burden.

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