Document Detail

Ring opening of benzo[a]pyrene in the germ-free rat is a novel pathway for formation of potentially genotoxic metabolites.
MedLine Citation:
PMID:  11112546     Owner:  NLM     Status:  MEDLINE    
The metabolism of benzo[a]pyrene (BP) is known to lead to a large number of oxygenated compounds, some of which can bind covalently to DNA. We have studied the integrated metabolism of BP in vivo in germ-free rats given (14)C-labeled BP. Urinary metabolites were separated into groups according to acidity using lipophilic ion exchangers. The groups were analyzed by mass spectrometry and were further fractionated by high-performance liquid chromatography. The fraction of urinary metabolites previously shown to contain N-acetylcysteine and glucuronic acid conjugates was found to contain derivatives of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid as major components. These compounds, which were identified by mass spectrometry and NMR, accounted for about 30% of the total metabolites in urine, demonstrating that, surprisingly, ring opening is a major pathway for metabolism of BP in the germ-free rat. The dicarboxylic acid may be excreted in urine as an ester glucuronide. By using the single cell gel electrophoresis or COMET assay, we were able to demonstrate that the anhydride of 7-oxo-benz[d]anthracene-3, 4-dicarboxylic acid was an efficient inducer of DNA damage. Taken together, these results indicate that the novel ring opening metabolic pathway may provide alternative mechanisms for the toxicity of BP.
Y Yang; W J Griffiths; M Nordling; J Nygren; L Möller; J Bergman; E Liepinsh; G Otting; J A Gustafsson; J Rafter; J Sjövall
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  39     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-16     Completed Date:  2001-01-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15585-91     Citation Subset:  IM    
Department of Medical Biochemistry & Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
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MeSH Terms
Bay-Region, Polycyclic Aromatic Hydrocarbon
Benzo(a)pyrene / chemistry*,  metabolism,  toxicity*
DNA Damage
Germ-Free Life
Reg. No./Substance:

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