Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars: Implications for risk assessment

Current methods to estimate the quantitative cancer risk of complex mixture s of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that ov erall potency can be derived from knowledge of the concentration of a few c arcinogenic components such as benzo[a]pyrene (B[a]P). Genotoxic damage, su ch as DNA adducts, is thought to be an essential aspect of PAH-induced tumo rigenesis 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 tum origenesis 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 rumors and tumor-free tissue and tumor outco mes were not predicted by either quantitation of total DNA adducts or by th e DNA adduct formed by B[a]P. These data suggest that risk assessments base d on B[a]P content may not predict accurately risk to human health posed by environmental PAH.