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Updated: Jul 14, 2026
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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
Summary
Homocysteine (Hcy) at high concentrations can cause genomic damage, specifically micronuclei formation, in vitro. However, Hcy also exhibits antioxidant properties, potentially mitigating oxidative stress.
Area of Science:
- Toxicology
- Genetics
- Cell Biology
Background:
- End-stage renal disease (ESRD) patients exhibit elevated genomic damage and cancer risk.
- Uremic toxins, such as homocysteine (Hcy), are implicated in ESRD-associated pathologies.
- Previous studies suggest a correlation between elevated Hcy levels and genomic damage.
Purpose of the Study:
- To investigate the in vitro genotoxic effects of homocysteine (Hcy).
- To assess Hcy's impact on DNA integrity, cell cycle, methylation, and oxidative stress markers.
Main Methods:
- Micronucleus tests and comet assays were conducted on L5178Y and HL60 cells.
- Cell cycle progression, DNA-cytosine-methylation, oxidative stress, and glutathione levels were analyzed.
- Cells were exposed to varying concentrations of Hcy and hydrogen peroxide (H2O2).
Main Results:
- Low millimolar Hcy induced micronuclei but did not increase comet assay-detected DNA damage.
- Hcy inhibited cell cycle progression in the S-phase.
- Hcy demonstrated antioxidant effects by protecting cells from H2O2-induced oxidative stress, correlating with increased glutathione levels.
Conclusions:
- Genotoxic effects of Hcy were observed only at high concentrations, suggesting a limited role in general ESRD genomic damage unless local accumulation occurs.
- Hcy's antioxidant capacity in ESRD patients requires further investigation.
- The study highlights a dual role of Hcy: potential genotoxicity at high levels and antioxidant properties.
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