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

INTRODUCTION: 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). METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.