Chemical Biomarkers of Exposure and Early Damage from Potentially Carcinogenic Airborne Pollutants

Abstract

Background: Epidemiology and laboratory studies support the conclusion that air pollution is carcinogenic to humans. Chemically specific biomarkers are useful for determining human exposure to, and metabolism of, potentially toxic and carcinogenic components of air pollution, and distinguishing exposures due to air pollution from those resulting from tobacco smoke.

Methods: Representative chemically specific biomarkers, quantified by mass spectrometry and related techniques, are discussed. The biomarkers are related to exposure to polycyclic aromatic hydrocarbons, volatile toxicants and carcinogens, oxidants, DNA damaging compounds, and metals found in polluted air.

Results: Quantifiable chemically specific biomarkers potentially useful in studies of air pollution carcinogenesis include urinary 1-hydroxypyrene, metabolites of benzo[a]pyrene, phenanthrene, benzene, 1,3-butadiene, acrolein, and crotonaldehyde, as well as products of oxidative damage such as urinary 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and F₂-isoprostanes, certain DNA adducts, and metals. Tobacco-specific metabolites such as cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol can be used to distinguish tobacco-related exposures from those resulting from air pollution.

Conclusions: The following validated chemically specific biomarkers are currently the optimal ones for use in studies of air pollution and cancer: urinary 1-hydroxypyrene, phenanthrene metabolites, S-phenyl mercapturic acid, urinary or blood Cd, 8-hydroxydeoxyguanosine and F₂-isoprostanes such as 8-iso-PGF_2α. This suite of biomarkers will reliably establish exposure to carcinogenic polycyclic aromatic hydrocarbons, benzene and Cd, and will also provide critical information on oxidative damage and inflammation, both of which are important in carcinogenesis.

Keywords: Air pollution; DNA adducts; carcinogenesis biomarkers; metals; oxidative damage; polycyclic aromatic hydrocarbons; volatile toxicants and carcinogens.

Fig. 1

Structures of main PAH metabolites discussed in this review.

Fig. 2

Metabolism of BaP and Phe to dihydrodiols, phenols, quinones and tetraols. P450, cytochrome P450; EH, epoxide hydrolase. AKR, aldo-keto reductases.

Figure 3.

Metabolic formation of SPMA from benzene. Benzene is converted to benzene oxide, catalyzed mainly by cytochrome P450 2E1. Benzene oxide is detoxified by reaction with glutathione (GSH), catalyzed by glutathione transferases (GSTs). Dehydration of the resulting intermediate yields phenyl glutathione, which is metabolized by the mercapturic acid pathway to the urinary metabolite and biomarker SPMA. Some of the undehydrated intermediate from the initial reaction with glutathione may also be processed by the mercapturic acid pathway giving 1-hydroxy-2-N-acetylcysteinyl)-1,2-dihydrobenzene; acid treatment of the urine sample converts this to SPMA.

Figure 4.

Metabolic formation of MHBMA from 1,3-butadiene

Figure 5.

Formation of 3-HPMA and HMPMA from acrolein (R = H) and crotonaldehyde (R = CH₃)