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Coxsackievirus B3 infection and PBDE exposure causes organ-specific effects on CYP-gene expression in the mouse.

Abstract
Common viral infections have been shown to change the tissue distribution of xenobiotics, including polybrominated diphenyl ethers (PBDEs). In previous studies, it has been shown that CYP2B gene expression is induced after PBDE exposure whereas coxsackievirus B3 (CBV3) infection suppresses the expression of CYP-gene expression in the liver. In the present study, CVB3 adapted to Balb/c mice was used to study the combined effects of infection and exposure to pure BDE-99 or the commercial mixture Bromkal on CYP1A1 and CYP2B expression in the lungs and pancreas on day 3 of the infection. The quantitative gene expression of virus, CYP1A1 and CYP2B was measured by real-time polymerase chain reaction (RT-PCR). PBDE exposure in the non-infected mice tended to increase CYP2B expression in the lungs but not in the pancreas. Infection in both non-exposed and PBDE-exposed mice increased CYP2B expression in the lungs but was non-detectable in the pancreas. In the non-infected mice PBDE exposure left the CYP1A1 expression unaltered in both the lungs and pancreas. Infection in both non-exposed and PBDE-exposed mice tended to decrease the gene expression of CYP1A1 in the lungs but to induce it in the pancreas. A correlation between the amount of virus and the gene expression of CYP2B was found in the lungs. However, no effects of PBDE on virus replication were observed in any organ. In conclusion, viral infection affects CYP-gene expression differently in the pancreas and lungs whereas PBDE-induced effects were not obvious. The organ-specific change in gene expression could explain a changed tissue distribution of xenobiotics during infection.
AuthorsMagnus Lundgren, Per Ola Darnerud, Ylva Molin, Hellmuth Lilienthal, Jonas Blomberg, Nils-Gunnar Ilbäck
JournalToxicology (Toxicology) Vol. 242 Issue 1-3 Pg. 91-9 (Dec 05 2007) ISSN: 0300-483X [Print] Ireland
PMID17964053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 2,2',4,4',5-brominated diphenyl ether
  • Halogenated Diphenyl Ethers
  • Hydrocarbons, Brominated
  • Phenyl Ethers
  • Bromkal 70
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1
Topics
  • Animals
  • Coxsackievirus Infections (enzymology, genetics, virology)
  • Cytochrome P-450 CYP1A1 (genetics, metabolism)
  • Cytochrome P-450 Enzyme System (genetics, metabolism)
  • Disease Models, Animal
  • Enterovirus B, Human (drug effects, pathogenicity)
  • Female
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Halogenated Diphenyl Ethers
  • Hydrocarbons, Brominated (toxicity)
  • Lung (drug effects, enzymology, virology)
  • Mice
  • Mice, Inbred BALB C
  • Pancreas (drug effects, enzymology, virology)
  • Phenyl Ethers (toxicity)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Virus Replication (drug effects)

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