Current methods to estimate the quantitative cancer risk of complex mixtures of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that overall potency can be derived from knowledge of the concentration of a few carcinogenic components such as benzo[a]pyrene (B[a]P). Genotoxic damage, such as DNA adducts, is thought to be an essential aspect of PAH-induced tumorigenesis and could be a biomarker for exposure useful for estimating risk. However, the role of B[a]P and the relationship of adduct formation in tumorigenesis have not been tested rigorously in models appropriate for human health risk assessment. Therefore, we directly compared tumor induction and adduct formation by B[a]P and coal tars in several experimental protocols, including one broadly accepted and used by regulators. We found that B[a]P content did not account for tumor incidences after exposure to coal tars. DNA adducts were found in both tumors and tumor-free tissue and tumor outcomes were not predicted by either quantitation of total DNA adducts or by the DNA adduct formed by B[a]P. These data suggest that risk assessments based on B[a]P content may not predict accurately risk to human health posed by environmental PAH.

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Abstract-The Galveston Bay estuary exhibited a contamination gradient for polynuclear aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons, and the comparative sensitivity of various biomarkers in fish from different bay locations were determined. Two fish species, hardhead catfish (Arius felis) and Atlantic croaker (Micropogon undulatus), were collected from four stations where sediment total PAHs ranged from 68 to Ͼ1,000 ng/g. The induction of cytochrome P4501A-(CYP1A-) dependent hepatic ethoxyresorufin-O-deethylase (EROD) activity, CYP1A mRNA levels, or CYP1A immunoreactive protein in hardhead catfish was highly variable in the field-collected fish and in fish dosed with up to 15 mg/kg benzo[a]pyrene (BaP). In contrast, significant differences were seen in biliary concentrations of naphthalene, phenanthrene, and BaP metabolites in hardhead catfish from polluted versus less polluted areas. In croakers taken from the same four Galveston Bay locations, EROD and glutathione Stransferase activities, immunoreactive CYP1A protein, biliary PAH metabolites, and PAH-DNA adducts were higher at the contaminated stations compared with less polluted locations. These studies suggest that the croaker is a good species for monitoring contaminants that induce CYP1A-mediated responses. Biliary PAH metabolites and PAH-DNA adducts were also sensitive indicators of exposure to PAH contamination in both species of fish.

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