Antioxidant intervention studies related to DNA damage, DNA repair and gene expression

Abstract

In human cells oxidatively modified nucleobases can be measured in the DNA and strand breaks can be detected by the Comet assay, optionally with the use of repair enzymes introducing breaks at oxidized bases. Oxidized bases and nucleosides from DNA repair, the nucleotide pool and cell turnover can be measured in urine. The excretion rate represents the average rate of damage in the body, whereas the level of oxidized bases in DNA is a concentration measurement in the specific cells. The expression of genes relevant for the defence against oxidative DNA damage, antioxidant and DNA repair enzymes can be assessed at the mRNA, protein and activity level. Functional assays can involve susceptibility to, and disappearance of, damage induced ex vivo in lymphocytes. Vitamins C and E, beta-carotene, coenzyme Q as well as various vegetables, fruit and carotenoid rich products, have been assessed with biomarkers mainly including damage in lymphocytes DNA by Comet and chemical assays and urinary excretion of oxidized bases and nucleosides. The basal levels as well as the reported effects of the interventions have been rather variable, possibly reflecting differences in the populations, regimens, functional correlates of the biomarkers as well as between laboratories and assays. However, the data suggest that a depleted state due to nutritional deficiency and/or an increased oxidative stress might facilitate demonstration of protective effects of antioxidants with respect to DNA damage. The effect of antioxidants on gene expression has been little studied in humans and only at the activity and protein level.