Polycyclic aromatic hydrocarbons: from metabolism to XXXX .

@entity1 @entity5 @entity2 @entity5874 @entity876
Excessive exposure to polycyclic aromatic hydrocarbons (PAHs) often results in @entity2 , a disease with the @entity5 mortality in the United States. After entry into the lung, PAHs induce phase I metabolic enzymes such as cytochrome P450 (CYP) monooxygenases, i.e. CYP1A1/2 and 1B1, and phase II enzymes such as glutathione S-transferases, UDP glucuronyl transferases, NADPH quinone oxidoreductases (NQOs), aldo-keto reductases (AKRs), and epoxide hydrolases (EHs), via the @entity5874 ( @entity5874 )-dependent and independent pathways. @entity1 can also be exposed to PAHs through diet, via consumption of charcoal broiled foods. Metabolism of PAHs through the CYP1A1/1B1/EH pathway, CYP peroxidase pathway, and AKR pathway leads to the formation of the active carcinogens diol-epoxides, radical cations, and o-quinones. These reactive metabolites produce DNA adducts, resulting in DNA mutations, alteration of gene expression profiles, and tumorigenesis. Mutations in xenobiotic metabolic enzymes, as well as polymorphisms of @entity5 suppressor genes (e.g. @entity876 ) and/or genes involved in gene expression (e.g. X-ray repair cross-complementing proteins), are associated with @entity2 susceptibility in @entity1 populations from different ethnicities, gender, and age groups. Although various metabolic activation/inactivation pathways, @entity5874 signaling, and genetic susceptibilities contribute to @entity2 , the precise points at which PAHs induce @entity5 initiation remain unknown. The goal of this review is to provide a current state-of-the-science of the mechanisms of @entity1 lung carcinogenesis mediated by PAHs, the experimental approaches used to study this complex class of compounds, and future directions for research of these compounds.
