Oxidative DNA damage in vivo: Relationship to age, plasma antioxidants, drug metabolism, glutathione-S-transferase activity and urinary creatinine excretion

Oxidative DNA modification has been implicated in development of certain ca ncers and 8-oxodG, the most abundant and mutagenic DNA modification, has fo r some time been considered a biomarker of this activity. Urinary excretion of 8-oxodG over 24h has been used to estimate the rate of damage to DNA, a nd animal studies have supported this rationale. Reported determinants incl ude tobacco smoking, heavy exercise, environmental pollution and individual oxygen consumption. Samples from three published studies were used to determine the association of urinary 8-oxodG excretion with age, plasma antioxidants, the glutathion e-S-transferase phenotype and the activity of the xenobiotic metabolising e nzyme CYP1A2. In the age range 35-65 years, age was not related to urinary 8-oxodG excretion, and there were no relations to either the glutathione-S- transferase phenotype or to the plasma antioxidants: vitamin C, alpha-tocop herol, beta-carotene, lycopene or coenzyme Q10. The activity of CYP1A2 show ed a significant correlation in two of the three studies, as well as a sign ificant correlation of 0.26 (p < 0.05) in the pooled data set. Regression a nalysis of CYP1A2 activity on 8-oxodG indicated that 33% increase in CYP1A2 activity would correspond to a doubling of 8-oxodG excretion. This finding needs to be confirmed in independent experiments. Spot morning urine samples can under certain circumstances be used to estim ate 8-oxodG excretion rate provided that creatinine excretion is unchanged tin paired experiments) or comparable tin un-paired experiments), as evalua ted from the correlation between 8-oxodG excretion in 24 h urine samples an d in morning spot urine samples corrected for creatinine excretion (r = 0.5 0, p < 0.05). We conclude that 8-oxodG excretion is determined by factors like oxygen con sumption and CYP1A2 activity rather than by factors like plasma antioxidant concentrations.