Pollution and the Genome: Genotoxic and Epigenetic Effects — Review

Environmental pollutants alter the genome via two chemically distinct routes (Hou et al., 2011). The first route involves covalent or oxidative modification of DNA, in which metabolically activated polycyclic aromatic hydrocarbons (PAHs) form bulky adducts, and transition metals and fine particulate matter (PM₂.₅) generate reactive oxygen species that produce 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and induce strand breaks. When these lesions coincide with impaired repair, they can lead to mutations, micronuclei, and chromosomal aberrations. The second route leaves the base sequence intact but alters how genes are read through DNA methylation, histone modification, and noncoding RNAs. This mini-review compares the evidence for both routes across five pollutant classes: ambient particulate matter, metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, and plasticizers (bisphenol A (BPA) and phthalates). The evidence is strongest for particulate matter, where human biomonitoring and cell and animal studies agree on oxidative DNA damage and methylation change. Prenatal exposure emerges as the most sensitive window, as methylation changes after prenatal lead, BPA, or phthalate exposure persist into childhood or adolescence in human cohorts and adulthood in mice (Goodrich et al., 2016; Khodasevich et al., 2024). The evidence is weaker for direct mutation endpoints in humans, pollutant-specific attribution within real mixtures, and transgenerational inheritance. We argue that single-assay studies cannot resolve these questions and propose a minimum biomarker panel that pairs a lesion marker, repair or instability marker, and epigenetic readout in the same subjects.