Marcela Rojas-Lemus¹, Patricia Bizarro-Nevares¹, Adriana E. González-Villalva¹, Nelly López-Valdéz¹, Norma Rivera-Fernández², Teresa I. Fortoul^1,

Ascorbate is part of the first-line antioxidant defense in biological fluids. It reacts with a variety of oxidants and is currently used in treatments to mitigate some diseases including cancer. However, this agent may cause DNA damage in healthy animal cells but the effects of ascorbate per se on biological systems have not yet been reported. Therefore, the aim of this study was to explore the ascorbate cytotoxic and genotoxic effects in cells from healthy mice (35 individuals in total, divided into 7 groups of 5 animals each and oral daily doses for 28 days). The results showed that ascorbate (at doses of 100, 150 and 225 mg/kg) causes a significant increase in micronuclei (MN) frequency (during the 4 weeks of administration: respectively 3, 4, 4 MN for every 2,000 reticulocytes, with a p value ≤ 0.05). The Pearson correlation index showed a positive and significant correlation r²= 0.9230; p= 0.0254) between the highest dose (225 mg) and the time of administration. The lowest dose that was administered in this study (50 mg/kg) did not produce MN however, a significant increase of DNA single-strand breaks was observed during all experimental time (in average, the migration index was 1.28 in comparison to 1.1 of the control group, with a p value ≤ 0.05). Cell death by cytotoxicity was not observed at any dose. These results indicate that the administration of ascorbate in healthy subjects is not innocuous and that its administration should be supervised because nowadays, the supplementation of large amounts of ascorbate without any medical supervision is frequent.

ascorbate, cell viability, retyculocytes, DNA damage, genotoxicity