Advances in Molecular Toxicology: Chapter Three. Genotoxicity of Polycyclic Aromatic Hydrocarbon Metabolites: Radical Cations and Ketones

Sushmita Sen · Jeffrey M. Field

aug 2013. · Advances in Molecular Toxicology 7. knjiga · Elsevier Inc. Chapters

O ovoj e-knjizi

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, so widespread that it is impossible for anyone to avoid exposure to them. They are the products of partial combustion, and exposure comes from the fossil fuels that we use to drive our cars, cook our food, warm our home, and fuel our industry. Other exposure comes from tobacco smoke and oil spills. PAHs are responsible for more cancers, primarily lung cancers, than any other carcinogen. The most studied PAHs are unsubstituted multi-ring structures. These compounds are not DNA reactive, and must be modified to become carcinogenic. Metabolic pathways modify PAH during the detoxification process. Three pathways have been extensively documented: the diol-epoxide pathway, the radical cation pathway, and the o-quinone pathway. Some PAHs are generated during combustion in oxygenated forms, usually as quinones. Quinones also form as PAHs are exposed to sunlight, for example, in an oil spill. These metabolic products damage DNA through distinct mechanisms: diol epoxides form bulky adducts with DNA, radical cations form depurinating adducts and quinones undergo futile redox cycling to generate reactive oxygen. Here, we discuss the evidence for these pathways in PAH carcinogenesis.