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, 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.
Goldstein
L S
LS
Electric Power Research Institute, Palo Alto, CA 94303, USA. lgoldste@epri.com
Weyand
E H
EH
Safe
S
S
Steinberg
M
M
Culp
S J
SJ
Gaylor
D W
DW
Beland
F A
FA
Rodriguez
L V
LV
D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D003033:Coal Tar / Q000633:toxicity*; D018736:DNA Adducts / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008815:Mice, Inbred Strains; D018570:Risk Assessment; D013997:Time Factors
D002273:Carcinogens; D018736:DNA Adducts; D001564:Benzo(a)pyrene; D003033:Coal Tar