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 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, su...

Full description

Saved in:
Bibliographic Details
Published in:Environmental health perspectives 1998-12, Vol.106 (suppl 6), p.1325-1330
Main Authors: Goldstein, Lawrence S., Eric H. Weyand, Safe, Stephen, Steinberg, Michael, Culp, Sandra J., Gaylor, David W., Beland, Frederick A., Rodriguez, Lewis V.
Format: Article
Language:English
Subjects:
Adducts
Administration, Oral
Animals
Benzo(a)pyrene - toxicity
Biomedical and Methodological Advances on Chemical Mixtures
Carcinogenicity Tests
Carcinogens - toxicity
Coal tar
Coal Tar - toxicity
DNA adducts
DNA Adducts - drug effects
Drug Interactions
Female
Forestomach
Injections, Intraperitoneal
Liver
Lungs
Mice
Mice, Inbred Strains
Polycyclic aromatic hydrocarbons
Risk analysis
Risk Assessment
Time Factors
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 PAHinduced 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.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.98106s61325