Chromium-Induced Lung Carcinogenesis Mechanisms

Hexavalent chromium (Cr(VI)) is recognised as a potent respiratory carcinogen when inhaled in occupational or environmental settings. Upon deposition in the airway epithelium, Cr(VI) readily enters cells via anion transporters and is sequentially reduced to reactive intermediates (Cr(V) and Cr(IV)) and ultimately to trivalent chromium (Cr(III)). These redox transitions generate reactive oxygen species (ROS) that inflict oxidative damage on DNA, proteins and lipids. Persistent oxidative stress promotes the formation of DNA adducts and strand breaks, overwhelms repair pathways and increases mutational burden. In parallel, Cr(VI) exposure induces epigenetic alterations such as promoter hypermethylation of tumour suppressor genes, histone tail modifications and microRNA repression, further disrupting cell-cycle control. Chronic injury also elicits a pro-inflammatory microenvironment, with elevated cytokine release, activation of survival signalling pathways (including Akt), and compensatory epithelial proliferation marked by upregulation of Ki-67. Over time, these intertwined processes of genotoxicity, epigenetic dysregulation, inflammation and aberrant repair drive the multistep progression from preneoplastic lesions to invasive carcinoma. Global analyses of occupational cohorts underscore the significance of cumulative exposure, while mechanistic studies reveal pivotal roles for redox imbalance and aberrant cell signalling in chromium-induced lung carcinogenesis.

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Chromium-Induced Lung Carcinogenesis Mechanisms publication trend

The graph below shows the total number of articles in chromium-induced lung carcinogenesis mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Hexavalent chromium (Cr(VI)): Highly soluble and toxic oxidation state of chromium that penetrates cells and undergoes reduction to generate reactive intermediates.

Reactive oxygen species (ROS): Unstable oxygen derivatives that damage DNA, proteins and lipids.

DNA adduct: Covalent attachment of a chemical to DNA bases, interfering with replication and repair.

Epigenetic modification: Heritable changes in gene expression without alteration to the DNA sequence, including DNA methylation and histone modification.

Inflammatory cytokines: Signalling proteins such as interleukins and tumour necrosis factor that mediate inflammatory and repair responses.

References

1. Mechanism of chromium-induced toxicity in lungs, liver, and kidney and their ameliorative agents. Biomedicine & Pharmacotherapy (2022).
2. Hexavalent-Chromium-Induced Oxidative Stress and the Protective Role of Antioxidants against Cellular Toxicity. Antioxidants (2022).
3. Lung Inflammation, Injury, and Proliferative Response after Repetitive Particulate Hexavalent Chromium Exposure. Environmental Health Perspectives (2009).
4. Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro. PLOS ONE (2014).