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1011918 
Journal Article 
Quantitative analysis of benzo[a]pyrene biotransformation and adduct formation in Ahr knockout mice 
Sagredo, C; Øvrebø, S; Haugen, A; Fujii-Kuriyama, Y; Baera, R; Botnen, IV; Mollerup, S 
2006 
1 
Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 
167 
3 
173-182 
English 
17049425 
WOS:000243046300002 
Benzo[a]pyrene (BP) is an ubiquitous environmental pollutant with potent mutagenic and carcinogenic properties. The Ah receptor (Ahr) is involved in the metabolic activation of BP and is therefore important in the induction of chemical carcinogenesis. In this study, the relationship between Ahr genotype and biotransformation of BP in internal organs was investigated in Ahr (+/+), Ahr (+/-) and Ahr (-/-) mice. The mice were treated with BP (100mg/kg) by gavage. Gene expression was measured after 24h by real-time RT-PCR and showed induction of Cyp1a1 in liver and lung, and Cyp1b1 in lung in both Ahr (+/+) and Ahr (+/-). No induction of the Cyp genes was observed in the Ahr (-/-). There was a significant basal expression of Cyp1b1 in the liver of all genotypes, and this expression was independent of the BP exposure. Analyzed by HPLC-fluorescence, there were increased levels of protein and DNA adducts, metabolites, conjugates and unmetabolized BP in the internal organs of Ahr (-/-) as compared to Ahr (+/+) and Ahr (+/-) mice. This may be partly explained by a delayed bioactivation of BP in the Ahr deficient mice. The BP metabolism observed in the Ahr (-/-) mice is also evidence of an Ahr independent biotransformation of BP. 
aryl hydrocarbon receptor; knockout mice; benzo[a]pyrene; benzo[alpyrene adducts; benzo[a]pyrene metabolites; cytochrome P450 
IRIS
• Benzo(a)pyrene (BaP)
     Considered
     Cited
          Toxicokinetics
          Genotoxicity