Oxidative DNA damage, antioxidants, and cancer

Abstract

Oxidised bases, such as 8‐oxo‐guanine, occur in cellular DNA as a result of attack by oxygen free radicals. The cancer‐protective effect of vegetables and fruit is attributed to the ability of antioxidants in them to scavenge free radicals, preventing DNA damage and subsequent mutation. Antioxidant supplements (e.g., β‐carotene, vitamin C) increase the resistance of lymphocytes to oxidative damage, and a negative correlation is seen between antioxidant concentrations in tissues and oxidised bases in DNA. Large‐scale intervention trials with β‐carotene have, however, led to increases in cancer. Recent measurements of the frequency of oxidised DNA bases indicate that earlier estimates were greatly exaggerated; there may be only a few thousand 8‐oxo‐guanines per cell. Convincing evidence for mutations resulting from oxidative damage, in tumours or cultured cells, is lacking. It seems that efficient antioxidant defences together with DNA repair maintain a steady‐state level of damage representing minimal risk to cell or organism. BioEssays 21:238–246, 1999. © 1999 John Wiley & Sons, Inc.