Molecular mechanisms of air pollution-induced carcinogenesis and the emerging role of microplastics.

Ambient air pollution is a major environmental carcinogen consisting of a complex mixture of particulate matter, gases, and adsorbed toxicants. Fine (PM2.5) and ultrafine (PM0.1) particles are of particular concern due to their capacity to penetrate deep into the lungs and translocate systemically, carrying carcinogens such as heavy metals, volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs). Exposure arises from traffic emissions, industrial activity, biomass combustion, and indoor sources, with inhalation as the primary route. Epidemiologic studies have firmly established associations between air pollution, particularly PM2.5 and increased risks of lung, bladder, breast, and hematologic cancers, even at concentrations below regulatory thresholds. Mechanistically, pollutant-induced carcinogenesis is driven by oxidative stress, DNA damage, epigenetic reprogramming, immune dysregulation, and impaired cell cycle control. Air pollution generates reactive oxygen species (ROS), disrupts mitochondrial function, alters DNA repair pathways, and modulates the expression of tumor suppressor genes through methylation and histone modifications. Prolonged inflammation and immune suppression in polluted tissue microenvironments further promote malignant transformation. Recent studies have shown increased interest in microplastics (MPs) as potential environmental carcinogens, given their unique physical properties and poorly characterized toxicological profiles. Preliminary findings indicate that microplastics are detectable in multiple cancer types and may correlate with distinct molecular alterations, suggesting a link to carcinogenesis and highlighting a critical future direction for environmental cancer research.