The amount of 8-hydroxydeoxyguanosine (8-OH-dG) excreted in urine can be used not only as an indicator of DNA repair capacity, but also as a potential marker of oxidative DNA damage. To clarify the oxidation-related factors, in consideration of cancer risk, this study investigated how urinary 8-OH-dG was associated with occupational and lifestyle factors in 372 healthy workers. The creatinine-adjusted urinary 8-OH-dG level was significantly higher in male subjects, smokers and drinkers compared with their counterparts. There were significant positive correlations of the 8-OH-dG level with average number of working hours, involvement in work, average number of cigarettes smoked, average volume of alcohol consumed and serum cortisol level, and there were significant negative correlations of the 8-OH-dG level with body mass index (BMI) and consumption of soybean products, rice and light-colored vegetables. Multiple regression analysis showed that average number of working hours and average number of cigarettes smoked were significant predictors of increased 8-OH-dG levels, whereas being female and BMI were significant predictors of decreased 8-OH-dG levels. Working hours, BMI and smoking were significant predictors of urinary 8-OH-dG in male subjects, whereas age and BMI were significant predictors in female subjects. We suggest that several occupational and lifestyle factors, particularly long working hours and cigarette smoking, are linked to the formation of 8-OH-dG in workers. (Cancer Sci 2005; 96: 600-606) I t is well-known and documented that reactive oxygen species (ROS) of the cellular metabolism can directly lead to oxidative damage to DNA, and can play an important role in various biological phenomena, including mutation, carcinogenesis, inflammation, aging and degenerative diseases.(1) 8-hydroxydeoxyguanosine (8-OH-dG, 7,8-dihydro-8-oxoguanosine) was first reported as causing oxidative DNA damage in 1984.(2) In cellular DNA, 8-OH-dG causes both mutagenesis and carcinogenesis, (3,4) and furthermore, it has been investigated in relation to a variety of diseases and hazards, particularly cancer and its risk factors.(3,4) For example, the formation of 8-OH-dG in various tissues or peripheral leukocytes as a result of administered carcinogens and other hazardous substances has been reported in many studies, (3,4) and increased 8-OHdG has been found in cancerous tissues.(5,6) Activities that have been linked to cancer, such as smoking and drinking, have also been reported to affect leukocyte or tissue 8-OHdG.(7-10) We provided the first evidence of a relationship between psychosocial stress and leukocyte 8-OH-dG levels in healthy workers, although sex differences also had an effect. (11)(12)(13) Taking these findings into consideration, we conclude that 8-OH-dG could be a useful marker for assessing cancer risk due to multiple risk factors.Tissue or leukocyte 8-OH-dG has been most frequently measured using a high performance liquid chromatography and electrochemical detector (HPLC-ECD) system because of its se...