Nickel-Induced Oxidative Stress and Genotoxicity

Nickel-induced oxidative stress arises when nickel ions catalyse the formation of reactive oxygen species, overwhelming cellular antioxidant defences and resulting in peroxidation of lipids, oxidation of proteins and strand breaks in DNA. Concurrently, nickel exerts genotoxic effects by directly binding to nucleic acids, displacing essential metal cofactors in DNA repair enzymes and altering chromatin structure through inhibition of histone demethylases and induction of DNA hypermethylation. Together, these events compromise nucleotide excision repair, base excision repair and double-strand break repair pathways, facilitating mutation accumulation and malignant transformation. Occupational and environmental exposures to nickel compounds—particularly nickel subsulfide and certain oxides—have been linked to elevated risks of lung and nasal tumours, dermatitis and systemic inflammation. At the cellular level, transported Ni2+ engages in Fenton-like chemistry to generate hydroxyl radicals and replaces iron in 2-oxoglutarate-dependent dioxygenases, disrupting epigenetic programmes and impairing genomic maintenance. The ubiquity of nickel in stainless steel, alloys and consumer products underpins its global significance, prompting research into environmental remediation, improved exposure limits and therapeutic strategies such as metal chelators and antioxidant supplementation to mitigate nickel-induced oxidative and genotoxic damage.

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Nickel-Induced Oxidative Stress and Genotoxicity publication trend

The graph below shows the total number of articles in nickel-induced oxidative stress and genotoxicity across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: An imbalance between pro-oxidant species and antioxidant defences, leading to cellular damage.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen, including superoxide and hydroxyl radicals.

Genotoxicity: The potential of a substance to damage genetic information in cells, causing mutations.

Epigenetic modifications: Heritable changes in gene expression not encoded in DNA sequence, such as DNA methylation and histone modification.

DNA repair pathways: Cellular mechanisms—such as nucleotide excision repair and homologous recombination—that detect and correct DNA lesions.

References

1. Concise Review of Nickel Human Health Toxicology and Ecotoxicology. Inorganics (2019).
2. Nickel Carcinogenesis Mechanism: DNA Damage. International Journal of Molecular Sciences (2019).
3. Nickel Ions Inhibit Histone Demethylase JMJD1A and DNA Repair Enzyme ABH2 by Replacing the Ferrous Iron in the Catalytic Centers*. Journal of Biological Chemistry (2009).
4. Distinct mechanisms of oxidative DNA damage induced by carcinogenic nickel subsulfide and nickel oxides.. Environmental Health Perspectives (2002).