Oxidative DNA damage, antioxidants, and cancer.
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., beta-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 beta-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.
Collins
A R
AR
Rowett Research Institute, Scotland, UK. a.collins@rri.sari.ac.uk
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage; D019587:Dietary Supplements; D006801:Humans; D008214:Lymphocytes; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010084:Oxidation-Reduction
D000975:Antioxidants