7.06 - Carcinogenic Polycyclic Aromatic Hydrocarbons

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion and are ubiquitous environmental pollutants. Epidemiological studies have confirmed that high occupational exposures to mixtures of PAHs lead to increased risks of lung, bladder, and skin cancers. Given that humans are exposed to complex mixtures of PAHs from pyrogenic and petrogenic sources, it is important to consider exposures to nitrated, alkylated, and oxygenated PAH derivatives (nitro-, alkyl-, and oxy-PAHs) to fully assess carcinogenic risk of environmental PAH mixtures. PAHs, nitro-PAHs and alkyl-PAHs are chemically inert and must be metabolically activated to exert their carcinogenic effects. Once converted to electrophilic and redox-active metabolites, PAHs and their derivatives promote formation of stable DNA adducts and oxidative DNA lesions. If DNA adducts evade repair, these lesions lead to mutations when they are bypassed by error-prone translesional DNA synthesis during cell replication. If somatic mutations occur in proto-oncogenes (K-Ras) and/or tumor suppressor genes (TP53), they can initiate neoplastic growth. PAHs, nitro-PAHs, alkyl-PAHs and their metabolites also have the ability to promote tumor growth and cancer progression through non-genotoxic mechanisms, and therefore act as complete carcinogens.