Polyaromatic Hydrocarbons

Poly aromatic hydrocarbons are a group of more than 100 ubiquitous environmental contaminants that occur naturally in coal, crude oil, and gasoline and are produced mainly from incomplete combustion of fossil fuels. PAHs are found in tobacco smoke, smoke from wood-burning stoves and fireplaces, and motor vehicle exhaust.2 Additionally, smoking or charbroiling meat can increase the formation of PAHs.29 Aside from occupational exposure, humans can potentially come into contact with PAHs through contaminated air, food, and water sources.2

One of the major routes of exposure to PAHs is via air pollution. It has been estimated that the daily intake for the general population of total PAHs inhaled is 207ng/m3.30 PAHs are believed to be present in urban air absorbed to respiratory particles.23 Once inhaled, these compounds can form covalent adducts with DNA, or are metabolized to quinones by CYP450 enzymes, namely CYP1A1, that initiates the formation of reactive oxygen species (ROS). The formation of ROS can also be stimulated by particle-induced inflammation.31

The consequence of these actions is thought to contribute to carcinogenesis via damage to DNA, initiation of cell proliferation, or alterations in cell-cycle control.

The carcinogenic potential of PAHs has been well established for decades, and evidence to date has resulted in many of these compounds being labeled as reasonably carcino-genic.2 The most striking data come from animal and in vitro studies of BaP, as well as occupationally exposed populations and cigarette smokers. Epidemiologic data supporting the development of cancer in the general (nonsmoking) population by inhaling these compounds is not as robust, but recent studies in conjunction with previous occupational exposure data suggest that exposure to PAHs in ambient air is a current concern. Presently, increases in markers of genotoxicity such as PAH-DNA adducts, PAH-protein adducts, cytogenetic damage, and urinary metabolites30 have been detected in several populations exposed to air pollution containing PAHs as a major contaminant in comparison to control regions.31 Lung tumors have also been detected in animals exposed to PAH-containing diesel exhaust.32 Data from in vitro studies show that c-myc expression, adduct formation, and cell-cycle progression are altered in lung epithelial cells exposed to PAHs33 and particulate matter containing PAH compounds.34 Li et al.35 showed a positive correlation between PAH content of particulate matter and the generation of ROS in rodent macrophages, whereas arsenic caused oxidative stress-induced apoptosis in rat lung epithelial cells.36

PAHs are also found in groundwater, usually as a result of industrial runoff into raw water supplies, and in leachates from coal tar and asphalt linings in water storage tanks and distribution lines. Overall, the levels of PAHs in drinking water supplies have been relatively low and, in general, are more abundant in food than water. A study by Kazerouni et al.29 showed the presence of PAHs in charbroiled meats and vegetables. They suggest that PAHs in plants are directly acquired from contaminated soil and air. Although animals that ingest PAHs in their diet get stomach cancers, future studies are required to determine if human populations are at increased risk for PAH-induced cancer through dietary exposures.2

The genotoxic mechanisms by which PAHs initiate cancer have been extensively explored since the discovery years ago that reactive metabolites of BaP could form DNA adducts. Based on this information, current biomarkers of PAH exposure have been limited to the detection of PAH metabolites and PAH-DNA adducts in blood, urine, and various tissues.37,38 Epigenetic mechanisms are not as well defined; however, recent studies indicate PAHs can alter cell signaling cascades that control cell communication, growth, and immune functions, which may lead to additional targets that would be useful as biomarkers of exposure. The expression of key signaling pathways including mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), nuclear factor kappa beta (NFkb), and protein kinase C (PKC) have all been shown to be affected by PAHs. More specifically, PAH-induced activation of MAPK, which resulted in altered cellular communication via gap junctions,39 suppressed various PKC isoforms,40 suppressed humoral and cell-mediated immunity,41 and induced AP-1 and NFkb, which may be involved in tumor-promoting effects.35 Additionally, PAHs have been shown to act through nuclear receptors, including estrogen receptors and the aryl hydrocarbon (Ah) receptor.42,43 Deciphering which signaling pathways are involved in PAH-

induced carcinogenesis is a complex task that is a current focus of researchers in the field.

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