Species-Dependent Differences in the Metabolic Activation of Polycyclic Aromatic Hydrocarbons in Cells in Culture

Polycyclic aromatic hydrocarbons are widespread environmental contaminants that require metabolic activation in order to induce biological effects1. One of the most widely studied carcinogenic hydrocarbons is benzo-(a)pyrene (BaP). Most pathways of BaP metabolism result in the production of metabolites that are detoxification products. However, a small proportion of the BaP metabolites are reactive derivatives that bind to DNA in cells and these DNA interactions are involved in the initiation of the cancer induction process1. Although these reactive metabolites cannot be isolated from cells so that their production can be quantitated, it is possible to measure their formation through detection of the DNA adducts they produce. The DNA serves as both a critical target for the “ultimate carcinogenic metabolites” and as a nucleophilic trapping agent for detection and measurement of these reactive electrophiles.