Homocysteine exerts genotoxic and antioxidative effects in vitro

Patients with end-stage renal disease suffer from increased genomic damage and cancer incidence. One possible reason is the accumulation of uremic toxins such as homocysteine (Hcy). Elevated Hcy levels – usually indicative of cardiovascular events – correlated with the genomic damage in cross-sectional studies. Therefore we investigated the genotoxic effects of Hcy in vitro. To analyse the genomic damage, micronucleus tests and the comet-assay were performed in L5178Y and HL60 cells. Additionally, the influence of Hcy on cell cycle progression, DNA-cytosine-methylation, oxidative stress levels and on the cellular glutathione content were determined. Low millimolar concentrations of Hcy-induced micronuclei in both cell lines but did not enhance the DNA damage observed with the comet-assay. Cell cycle progression was inhibited in S-phase, while DNA-cytosine-methylation remained unchanged. Furthermore, Hcy protected cells challenged with H 2O 2 from oxidative stress. This was accompanied by an increased cellular glutathione level. Since the genotoxic effect was limited to high Hcy concentrations, a contribution of Hcy to the enhanced genomic damage in end-stage renal disease patients would only be conceivable upon local Hcy accumulation. Whether the detected antioxidant capacity of Hcy is relevant for any situation in patients remains to be elucidated.