Oral Benzo[a]pyrene in Cyp1 Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate

@article{Uno2006OralBI,
  title={Oral Benzo[a]pyrene in Cyp1 Knockout Mouse Lines: CYP1A1 Important in Detoxication, CYP1B1 Metabolism Required for Immune Damage Independent of Total-Body Burden and Clearance Rate},
  author={Shigeyuki Uno and Timothy P. Dalton and Nadine Dragin and Christine Perdan Curran and Sandrine Derkenne and Marian L Miller and Howard G. Shertzer and Frank J. Gonzalez and Daniel W. Nebert},
  journal={Molecular Pharmacology},
  year={2006},
  volume={69},
  pages={1103 - 1114}
}
CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene, to reactive intermediates associated with toxicity, mutagenesis, and carcinogenesis. Paradoxically, however, Cyp1a1-/- knockout mice are more sensitive to oral benzo[a]pyrene exposure, compared with wild-type Cyp1a1+/+ mice (Mol Pharmacol 65:1225, 2004). To further investigate the mechanism for this enhanced sensitivity, Cyp1a1-/-, Cyp1a2-/-, and Cyp1b1-/- single-knockout, Cyp1a1/1b1… 
Polycyclic Aromatic Hydrocarbon (PAH)-Induced Pulmonary Carcinogenesis in Cytochrome P450 (CYP) 1A1- and 1A2-null Mice: Roles of CYP1A1 and CYP1A2.
TLDR
The hypothesis that mice lacking the genes for Cyp 1a1 or Cyp1a2 will display altered susceptibilities to PAH-induced pulmonary carcinogenesis is tested and the need to develop novel CYP1A1 inhibitors to mitigate human lung cancer is supported.
Vitamin D Receptor Activation Enhances Benzo[a]pyrene Metabolism via CYP1A1 Expression in Macrophages
TLDR
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Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract.
Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease caused by Western diet containing benzo[a]pyrene in mice.
  • S. Uno, D. Nebert, M. Makishima
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    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2018
Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice.
TLDR
Hepatic CYP enzymes appear to be more important for detoxification of BaP in vivo, despite being involved in its metabolic activation in vitro, revealing an apparent paradox.
Inhibition of aryl hydrocarbon receptor transactivation and DNA adduct formation by CYP1 isoform-selective metabolic deactivation of benzo[a]pyrene.
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