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Updated: Jul 14, 2026

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Homocysteine exerts genotoxic and antioxidative effects in vitro
1Institute of Pharmacology and Toxicology, University of Wuerzburg, Versbacherstrasse 9, 97078 Wuerzburg, Germany. Kristin.fink@email.de
Introduction:
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.
Methods:
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.
Results:
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(2)O(2) from oxidative stress. This was accompanied by an increased cellular glutathione level.
Conclusion:
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.
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