Loft S, Vistisen K, Ewertz M, Tjønneland A, Overvad K, Poulsen H E
Department of Pharmacology, University of Copenhagen, Denmark.
Carcinogenesis. 1992 Dec;13(12):2241-7. doi: 10.1093/carcin/13.12.2241.
Oxidative DNA damage may be implicated in ageing, carcinogenesis and other degenerative diseases. Oxidative DNA damage can be assessed in humans in vivo from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8OHdG). We investigated factors influencing the excretion of 8OHdG in 24 h urine from 83 randomly selected healthy subjects (52 women) aged 40-64 years. For 2 weeks prior to urine collection the subjects kept a weighed diet record. 8OHdG was quantified by an automatic three-dimensional HPLC analysis with electrochemical detection. The 8OHdG excretion was 252 +/- 103 (mean +/- SD) pmol kg body weight/24 h with a range from 78 to 527. Multiple regression analysis identified three factors, smoking, body mass index (BMI) and gender, as significant predictors of the 8OHdG excretion. In 30 smokers the 8OHdG excretion was 320 +/- 99 pmol/kg/24 h opposed to 213 +/- 84 pmol/kg/24 h in 53 non-smokers. According to multiple regression analysis smokers excreted 50% (31-69%; 95% confidence interval) more 8OHdG than non-smokers. In 52 women the 8OHdG excretion was 240 +/- 106 pmol/kg/24 h opposed to 271 +/- 96 pmol/kg/24 h in 31 men. According to the multiple regression analysis men excreted 29% (10-48%) more 8OHdG than women. According to multiple regression analysis the 8OHdG excretion decreased with 4% (2-6%) per increment in BMI measured in kg/m2. The dietary distribution of energy demonstrated no important predictive value with respect to 8OHdG excretion. The intake of the antioxidant vitamins C and E and of vitamin A equivalents, including beta-carotene, was not associated with 8OHdG excretion. The results suggest that smoking increases oxidative DNA damage by approximately 50%. This effect implies potential serious health effects adding to the other well-known health hazards of smoking. The higher 8OHdG excretion in men and lean subjects may be related to a higher rate of metabolism with increased availability of reactive oxygen species. The apparent 7-fold individual variation in oxidative DNA damage carries implications regarding the rate of ageing and the risk of cancer and other degenerative diseases. The excretion of 8OHdG into urine offers a valuable tool for testing such hypotheses in humans.
氧化性DNA损伤可能与衰老、致癌作用及其他退行性疾病有关。可通过检测DNA修复产物8-羟基脱氧鸟苷（8OHdG）的尿排泄量，在人体活体中评估氧化性DNA损伤。我们对83名年龄在40 - 64岁之间随机选取的健康受试者（52名女性）24小时尿液中8OHdG的排泄影响因素进行了研究。在收集尿液前的2周内，受试者记录了称重饮食情况。8OHdG通过带有电化学检测的自动三维高效液相色谱分析进行定量。8OHdG排泄量为252±103（均值±标准差）pmol/千克体重/24小时，范围在78至527之间。多元回归分析确定了吸烟、体重指数（BMI）和性别这三个因素是8OHdG排泄的显著预测因子。30名吸烟者的8OHdG排泄量为320±99 pmol/千克/24小时，而53名不吸烟者为213±84 pmol/千克/24小时。根据多元回归分析，吸烟者排泄的8OHdG比不吸烟者多50%（31 - 69%；95%置信区间）。52名女性的8OHdG排泄量为240±106 pmol/千克/24小时，31名男性为271±96 pmol/千克/24小时。根据多元回归分析，男性排泄的8OHdG比女性多29%（10 - 48%）。根据多元回归分析，以千克/平方米为单位测量的BMI每增加，8OHdG排泄量下降4%（2 - 6%）。能量的饮食分布对8OHdG排泄没有重要的预测价值。抗氧化维生素C、E以及包括β-胡萝卜素在内的维生素A当量的摄入量与8OHdG排泄无关。结果表明，吸烟使氧化性DNA损伤增加约50%。这种影响意味着除了吸烟的其他众所周知的健康危害外，还可能产生潜在的严重健康影响。男性和瘦人较高的8OHdG排泄量可能与代谢率较高以及活性氧物质的可用性增加有关。氧化性DNA损伤明显的7倍个体差异对衰老速度以及患癌症和其他退行性疾病的风险具有影响。8OHdG排泄到尿液中为在人体中验证此类假设提供了一种有价值的工具。
