Humans and other mammals are equipped with a sophisticated machinery to handle carcinogens and other xenobiotic compounds, present in the cigarette smoke (CS). The metabolism of xenobiotics includes oxidative reactions by phase I enzymes that convert lipophilic chemical compounds into their hydrophilic forms, followed by phase II conjugation enzymes, and finally the phase III membrane transporters 1. The second and the last play a role in the elimination of xenobiotic metabolites 1. The most prominent phase I enzymes are cytochrome P450s (also known as CYPs) that detoxify or activate xenobiotic compounds 1.
The roles of various CYPs on the metabolism of CS toxicants have been discussed elsewhere in great detail 2-6.
One central player in the xenobiotic metabolism is the transcription factor aryl hydrocarbon receptor (AHR) that is activated by xenobiotic compounds and regulates the expression of several target genes (e.g., CYP1A1, CYP1B1, among others).
Normally, the levels of CYPs in the lung are expressed at trace levels, but they are induced upon CS exposure 7. Studies have reported that bronchial tissues of smokers exhibit higher levels of CYPs (e.g., CYP1A1 and CYP1B1) as compared to nonsmokers 8-12. Smoking cessation can reverse the induction of CYP expression upon smoking 8.
Also in the liver, CS constituents can induce several liver xenobiotic metabolizing enzymes. These include cytochrome P450 enzymes and glutathione S-transferases, enzymes whose genetic polymorphisms have, in turn, been associated with a higher risk of CS-related diseases 13-16.