Polycyclic Aromatic Hydrocarbons Multiple Metabolic Pathways and the DNA Lesions Formed

Polycyclic Aromatic Hydrocarbons Multiple Metabolic Pathways and the DNA Lesions Formed 

Polycyclic aromatic hydrocarbons (PAHs) represent a class of compounds that contain two or more fused benzene rings. They are environmental pollutants and the most ubiquitous, benzo[a]pyrene (B[a]P), has been upgraded by the International Agency for Research on Cancer to a Group 1 or known human carcinogen [1]. PAHs are products of fossil fuel combustion they are a component of fine particulate matter (size 2.5pm) and as a consequence contaminate the air we breathe, the soil and water supply, and enter the food chain [2, 3]. They are also introduced artificially into smoked, cured, and barbecued food [4, 5], Finally, they are present as a complex mixture in tobacco smoke and second-hand smoke, and are suspect causative agents in human lung cancer [6]. 

The Chemical Biology of DNA Damage. Edited by Nicholas E. Geacintov and Suse Broyde 2010 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32295-4 

Knowing which pathways of PAH activation prevail provides a rationale for the detection and quantitation of PAH-derived DNA adducts in population-based studies. Measurement of these adducts provides a method for biomonitoring PAH exposure and provides a risk assessment for susceptibility to diseases such as lung cancer. This could be particularly useful if it is assumed that there is a correlation between DNA adducts, mutational load, and, ultimately, tumor formation. 

Detection and quantitation of PAH-derived DNA adducts requires authentic synthetic standards to act as internal standards and therefore a knowledge of adduct structure. Adduct structure can often be used to provide information on the mechanism of PAH activation that must have occurred. Unfortunately, this is quite challenging since PAH-DNA adducts can be difficult to detect and quantitate since they may be present in only 1 108 nucleotides. State-of-the art methods requiring stable isotope dilution liquid chromatography/multiple reaction monitoring/mass spectrometry (LC/MRM/MS) are necessary to provide sufficient sensitivity to detect these adducts reliably. Additionally, PAH-DNA adducts have different rates of repair and yield different rates of mutation. Thus, each adduct must be assessed so that it can be ranked according to its half-life and miscoding potential. 

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