Genotoxicity and Proteotoxicity of Arsenic: Mechanisms, Clinical Implications, and Therapeutic Challenges

Arsenic is a ubiquitous environmental metalloid with dual characteristics-acting as both a potent toxin and an effective therapeutic agent. Chronic exposure to inorganic arsenic species, arsenite [As(III)] and arsenate [As(V)], is associated with multiple cancers and systemic diseases, whereas Arsenic Trioxide (ATO) demonstrates strong anticancer efficacy, particularly in Acute Promyelocytic Leukemia (APL).

A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar to review epidemiological, experimental, and clinical studies. Inclusion criteria focused on works addressing arsenic-induced genotoxicity, proteotoxicity, and therapeutic applications. Data were extracted regarding molecular mechanisms, biomarkers, and mitigation strategies.

Arsenic induces oxidative stress, DNA damage, and epigenetic alterations, leading to genomic and proteomic instability. Clinical evidence indicates ATO achieves remission rates exceeding 90% in APL by degrading the PML-RARα oncoprotein. Emerging nanotechnology and precision medicine approaches enhance drug delivery, reduce systemic toxicity, and support targeted therapy.

Arsenic's paradoxical behavior is dose- and context-dependent. While chronic lowlevel exposure drives carcinogenesis, controlled pharmacologic use offers therapeutic benefit. Integration of omics technologies and nanocarriers can refine their safety and clinical applicability.

Arsenic exemplifies the intersection of toxicity and therapy. Understanding its genotoxic and proteotoxic mechanisms supports the development of safer, precision-based interventions and expands its potential as a therapeutic agent in modern oncology.