Benzo[a]pyrene Toxicity and Inflammatory Disease

Abstract

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in cigarette smoke, grilled meats and byproducts of industrial incineration. BaP exposure through cigarette smoking has been implicated in the pathogenesis of lung and head-and-neck cancers and atherosclerosis. BaP inhalation activates the aryl hydrocarbon receptor (AHR), a transcription factor that induces expression of genes involved in xenobiotic metabolism. BaP can be metabolized to active compounds that form DNA adducts and induce the production of reactive oxygen species in cells, leading to inflammatory cytokine production. Polymorphisms of cytochrome P450 enzymes that are induced by AHR and function in BaP metabolism have been reported to confer increased risk of rheumatoid arthritis in Asian populations. AHR induces T cell differentiation to both immunoregulatory and autoimmune/inflammatory lineages. Dynamic metabolic activation of BaP and cell type-specific AHR activation may influence AHR-regulated immune responses. An improved understanding of AHR function should provide pharmacologic approaches to BaP detoxification useful in the prevention of diseases associated with environmental pollutants, such as rheumatoid arthritis.