Homocysteine exerts genotoxic and antioxidative effects in vitro

IntroductionPatients 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.MethodsTo 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.ResultsLow 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 H2O2 from oxidative stress. This was accompanied by an increased cellular glutathione level.ConclusionSince 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.