| Tumors and DNA Adducts in Mice Exposed to Benzo[a]pyrene and Coal Tars: Implications for Risk Assessment Lawrence S. Goldstein,1 Eric H. Weyand,2 Stephen Safe,3 Michael Steinberg,3 Sandra J. Culp,4 David W. Gaylor,4 Frederick A. Beland,4 and Lewis V. Rodriguez5 1Electric Power Research Institute, Palo Alto, California
2College of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, New Jersey
3Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas
4National Center for Toxicological Research, Jefferson, Arkansas
5Department of Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, Texas Abstract
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. -- Environ Health Perspect 106(Suppl 6) :1325-1330 (1998) . http://ehpnet1.niehs.nih.gov/docs/1998/Suppl-6/1325-1330goldstein/abstract.html Key words: coal tar, benzo[a]pyrene, benzpyrenediolepoxide, DNA adducts, infant mouse, A/J mouse, liver tumors, lung tumors, forestomach tumors, risk assessment
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