The Effects of Vitamin C on Oxidative DNA Damage and Mutagenesis

Abstract

DNA damage induced by reactive oxygen species is involved in mutagenesis and generation of mutation-related diseases, including cancer. Therefore, study of antigenotoxic potential of antioxidants is of great importance for protection of human health. Vitamin C is well known as a potent antioxidant, but its prooxidative effects have also been reported. In this work, antigenotoxic properties of vitamin C in E. coli K12, E. coli WP2 and S. cerevisiae D7 reversion assays, as well as in S. cerevisiae comet assay were examined. t-Butyl hydroperoxide (t-BOOH) was used to induce oxidative mutagenesis, and hydrogen peroxide (H2O2) was used to induce DNA strand breaks in the comet assay. Vitamin C reduced t-BOOH-induced and spontaneous mutagenesis in repair proficient and mismatch repair (MMR) deficient strains of E. coli K12 respectively, as well as t-BOOH-induced mutagenesis in S. cerevisiae D7 strain. However, in E. coli K12 strains that carry plasmid with microsatellite sequences, treatment with vitamin C slightly stimulated microsatellite instability. Vitamin C also showed mutagenic effects in WP2 oxyR strain, probably due to its prooxidative potential, amplified in the strain deficient in antioxidative defense. In the yeast comet assay, contradictory results were obtained: while low concentration (0.05 mM) of vitamin C inhibited oxidative damage, higher concentrations (0.1–10 mM) stimulated it. The obtained results indicate that vitamin C can exhibit antigenotoxic or genotoxic effects, depending on the dose, genetic background and other experimental conditions.

Keywords

• antigenotoxic potential
• vitamin C
• E. coli
• S. cerevisiae
• reversion assay
• yeast comet assay