Aromatic mutagens

Aromatic mutagens are a broad class of chemical compounds, including polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs), known for their ability to induce genetic mutations and promote carcinogenesis (IARC, 2010). These substances are common environmental pollutants found in tobacco smoke, industrial emissions, and charred foods (PubChem, 2024). Biologically, most aromatic mutagens are pro-carcinogens that require metabolic activation by Phase I enzymes, such as Cytochrome P450 1A1 (CYP1A1), to become reactive electrophiles (Nebert & Dalton, 2006). Once activated, they can form bulky covalent DNA adducts or intercalate between base pairs, leading to permanent mutations during DNA replication (Xue & Warshawsky, 2005). While they are not therapeutic targets in the traditional sense, they interact significantly with the Aryl hydrocarbon receptor (AhR), which mediates the cellular response to environmental toxins (Denison & Nagy, 2003). Understanding these molecules is critical for developing chemopreventive strategies that aim to inhibit metabolic activation or enhance detoxification pathways like those involving Glutathione S-transferases (Shimada, 2006).

Other names

Polycyclic aromatic hydrocarbonsPAHsHeterocyclic aromatic aminesHAAsArylaminesNitroarenesGenotoxic aromatics

Chemopreventive agents act by inhibiting Cytochrome P450-mediated metabolic activation and inducing Phase II detoxification enzymes to facilitate the excretion of aromatic mutagens.