Carcinogenesis

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Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index

Steffen Loft, Kirsten Vistisen, Marianne Ewertz ¹, Anne Tjønneland ¹, Kim Overvad ² and Henrik Enghusen Poulsen

Department of Pharmacology, University of Copenhagen Juliane Maricsvej 20, DK-2100 Copenhagen Ø
¹Institute of Cancer Epidemiology, Danish Cancer Registry Danish Cancer Society, Rosenvaengets Hovedvej 35, Box 839, DK-2100 Copenhagen Ø
²Institute of Epidemiology and Social Medicine, University of Arhus HØegh-Guldbergs Gade 8, DK-8000 Arhus C, Denmark

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 ± % 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 ß-carotene, was not associated with 8OHdG excretion. The results suggest that smoking increases oxidative DNA damage by 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.

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