Benzo[a]pyrene Carcinogenic

Benzo[a]pyrene is one of the most carcinogenic of the aromatic hydrocarbons. This hydrocarbon is formed whenever an organic compound undergoes incomplete combustion. For example, benzo[a]pyrene is found in cigarette smoke, automobile exhaust, and charcoal-broiled meat. Several arene oxides can be formed from benzo[a]pyrene. The two most harmful are the 4,5-oxide and the 7,8-oxide. It has been suggested that people who develop lung cancer as a result of smoking may have a higher than normal concentration of cytochrome P450 in their lung tissue. The 4,5-oxide is harmful because it forms a carbocation that cannot be stabilized by electron delocalization without destroying the aromaticity of an adjacent benzene ring. Thus, the carbocation is relatively unstable, so the epoxide will tend not to open until it is attacked by a nucleophile. The 7,8-oxide is harmful because it reacts with water to form a diol, which then forms a diol epoxide. The diol epoxide does not readily undergo rearrangement (the harmless pathway), because it opens to a carbocation that is destabilized by the electron-withdrawing OH groups. Therefore, the diol epoxide can exist long enough to be attacked by nucleophiles (the carcinogenic pathway).