Collins A R
Rowett Research Institute, Scotland, UK.
Bioessays. 1999 Mar;21(3):238-46. doi: 10.1002/(SICI)1521-1878(199903)21:3<238::AID-BIES8>3.0.CO;2-3.
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.
诸如8-氧代鸟嘌呤等氧化碱基是由于氧自由基的攻击而在细胞DNA中出现的。蔬菜和水果的防癌作用归因于其中的抗氧化剂清除自由基的能力，从而防止DNA损伤及随后的突变。抗氧化剂补充剂（如β-胡萝卜素、维生素C）可增强淋巴细胞对氧化损伤的抵抗力，并且在组织中的抗氧化剂浓度与DNA中的氧化碱基之间存在负相关。然而，使用β-胡萝卜素进行的大规模干预试验却导致癌症发病率上升。最近对氧化DNA碱基频率的测量表明，早期的估计被大大夸大了；每个细胞中可能只有几千个8-氧代鸟嘌呤。在肿瘤或培养细胞中，缺乏氧化损伤导致突变的确凿证据。似乎有效的抗氧化防御机制与DNA修复共同维持着一个稳定的损伤水平，对细胞或生物体的风险降至最低。
