Metabolism and mutagenicity of dibenzo(a,e)pyrene and the very potent environmental carcinogen dibenzo(a,l)pyrene

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00018a014· OSTI ID:5110670

Devanesan, P D; Cremonesi, P; Nunnally, J E; Rogan, E G; Cavalieri, E L ^[1]

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1. Univ. of Nebraska, Omaha (United States)

Dibenzo(a,l)pyrene (DB(a,l)P) is one of the most potent carcinogens ever tested in mouse skin and rat mammary gland. DB(a,l)P is present in cigarette smoke and, presumably, in other environmental pollutants. Metabolism and mutagenicity studies of this compound compared to the weak carcinogen dibenzo(a,e)pyrene (DB(a,e)P) can provide preliminary evidence on its mechanism of carcinogenesis. The mutagenicity of DB(a,l)P, DB(a,e)P, and benzo(a)pyrene (BP) was compared in the Ames assay with Aroclor-induced rat liver S-9. BP was the strongest mutagen. In strain TA100, DB(a,l)P were marginally mutagenic. In strain TA98 both compounds were mutagenic, and DB(a,l)P induced more than twice as many revertants as DB(a,e)P. The mutagenicity of DB(a,l)P does not correlate with its carcinogenicity, since DB(a,l)P is a much stronger carcinogen, but a much weaker mutagen, than BP. The NADPH-support metabolism of DB(a,e)P and DB(a,l)P was conducted with uninduced and 3-methylcholanthrene-induced rat liver microsomes. Metabolites were analyzed by reverse-phase HPLC and identified by NMR, UV, and mass spectrometry. Uninduced microsomes produced only traces of metabolites with either compound. The major metabolites of DB(a, l)P with induced microsomes were DB(a,l)P 8, 9-dihydriol, DB(a,l)P 11,12-dihydrodiol, 7-hydroxyDB(a,l)P, and a DB(a,l)P dione. The metabolites of DB(a,e)P with induced microsomes were DB(a,e)P 3,4-dihydrodiol, 3-hydroxyDB(a,e)P, 7-hydroxyDB(a,e)P, and 9-hydroxyDB(a,e)P. Some of these metabolites are very useful in assessing possible pathways of activation in the initiation of cancer.

• OSTI ID: 5110670
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 3:6; ISSN 0893-228X; ISSN CRTOE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AEROSOLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL PATHWAYS
BODY
CARCINOGENS
CELL CONSTITUENTS
CHEMICAL REACTION KINETICS
CHROMATOGRAPHY
COLLOIDS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DISPERSIONS
GLANDS
HYDROCARBONS
IN VIVO
KINETICS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
MAMMARY GLANDS
MASS SPECTRA
METABOLISM
METABOLITES
MICE
MICROSOMES
MOLECULAR STRUCTURE
MUTAGEN SCREENING
MUTAGENESIS
MUTANTS
NMR SPECTRA
ORGANIC COMPOUNDS
ORGANS
RATS
REACTION KINETICS
RESIDUES
REVERTANTS
RIBOSOMES
RODENTS
SCREENING
SEPARATION PROCESSES
SKIN
SMOKES
SOLS
SPECTRA
TOBACCO SMOKES
ULTRAVIOLET SPECTRA
VERTEBRATES