Does mercury bind sulfhydryl groups and drive oxidative DNA damage?

Mercury’s high affinity for sulfur- and selenium-containing cellular targets provides a coherent, experimentally supported route from exposure to oxidative stress and DNA injury. The evidence is strongest for biochemical mechanisms and experimental models, particularly for Hg(II) and methylmercury.

Chemical and cellular mechanisms

• Hg(II) and methylmercury preferentially bind thiolate groups on cysteine and glutathione; methylmercury can exchange among glutathione, low-molecular-weight thiols, and protein cysteines.
• This interaction can deplete reduced glutathione (GSH), lower the GSH:GSSG ratio, and inhibit thiol/selenol-dependent antioxidant enzymes. In purified rat thioredoxin reductase, HgCl₂ inhibited activity with an IC₅₀ of 7.2 nM after 5 minutes; 2.5 μM Hg²⁺ reduced thioredoxin reductase activity by about 45% and glutathione peroxidase by about 30%.

Mitochondrial dysfunction and ROS

• Methylmercury impairs mitochondrial respiration and oxidative phosphorylation, with associated glutathione oxidation, hydroperoxide formation, and lipid peroxidation. In SH-SY5Y neuroblastoma cells, 1 μM methylmercury increased intracellular ROS; lack of this response in mitochondrial-DNA-depleted cells supports a mitochondrial ROS source.
• Loss of GSH, glutathione peroxidase, and thioredoxin reductase function reduces peroxide detoxification, while mitochondrial injury can further amplify superoxide and hydrogen-peroxide–related oxidative stress.

Oxidative DNA damage

• Primary-cell studies report dose-related increases in ROS, 8-oxo-dG, and abasic DNA lesions after methylmercury exposure. Human neural progenitor-cell work similarly links methylmercury with mitochondrial dysfunction and oxidative mitochondrial-DNA damage.
• Higher urinary or blood-cell 8-OHdG has been observed in mercury-exposed populations, but this biomarker is not mercury-specific and does not establish an individual clinical risk or exposure threshold.

Bottom line

• The claim is scientifically supported: mercury binding to thiols/selenols can compromise antioxidant and mitochondrial defenses, increase ROS, and plausibly cause oxidative DNA damage. The mechanistic evidence is strong; direct human dose–response evidence for this full pathway is less specific.