URINARY-EXCRETION OF 5-(HYDROXYMETHYL)URACIL IN HEALTHY-VOLUNTEERS - EFFECT OF ACTIVE AND PASSIVE TOBACCO-SMOKE

The urinary excretion of 5-(hydroxymethyl)uracil (5-HMUra), one of the major oxidative modifications of thymine, was investigated in 134 hea lthy volunteers living in North Italy. Overnight urine was collected, and a questionnaire was completed on smoking habits and exposure to en vironmental tobacco smoke (ETS), 5-HM Ura was analyzed by GC/MS, follo wing urine purification by HPLC, 5-HMUra excretion showed an approxima tely normal distribution, ranging from 0.08 to 0.84 (mean 0.44) nmoles /kg/8 hr and from 3.2 to 18.7 (mean 8.5) nmoles/mmoles creatinine. 5-H MUra excretion was significantly higher in women than in men and in sm okers than in non-smokers when results were expressed as the ratio to creatinine, Slightly higher levels of 5-HMUra excretion, expressed as nmoles/mmoles creatinine, were also found in subjects highly exposed t o ETS, monitored either as the number of hours of exposure or as the n umber of smokers in the workplace and at home. Our results show that t he urinary excretion of 5-HMUra is higher than that of other oxidized nucleobases, including 8-oxo-7,8-dihydroguanine, and can be slightly m odified by environmental factors such as tobacco smoke, These findings suggest that measurement of urinary excretion of 5-HMUra could be use ful as a biomarker of oxidative DNA damage and repair, though further research is needed to support these data. (C) 1991 Wiley-Liss, Inc.