Carcinogenesis Advance Access originally published online on January 16, 2004
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Carcinogenesis, Vol. 25, No. 5, 793-799,
May 2004
Carcinogenesis vol.25 no.5 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Benzo[a]pyrene phenols are more potent inducers of CYP1A1, CYP1B1 and COX-2 than benzo[a]pyrene glucuronides in cell lines derived from the human aerodigestive tract
1 Memorial Sloan-Kettering Cancer Center, Head and Neck Service, Department of Surgery, New York, NY 10021, USA, 2 Weill Medical College of Cornell University, Department of Medicine, New York, NY 10021, USA, 3 Weill Medical College of Cornell University, Department of Otorhinolaryngology, New York, NY 10021, USA, 4 Weill Medical College of Cornell University, Department of Cardiothoracic Surgery, New York, NY 10021, USA, 5 CADRG, DCP, National Cancer Institute, Bethesda, Maryland, USA, 6 H. Lee Moffitt Cancer Center and Research Institute, Divisions of Cancer Control and Molecular Oncology, Tampa, Florida, USA and 7 Strang Cancer Prevention Center, New York, NY 10021, USA
8 To whom correspondence should be addressed Email: ajdannen@med.cornell.edu
Abbreviations: B[a]P, benzo[a]pyrene; COX, cyclooxygenase; 3-OH-B[a]P, 3-hydroxy-benzo[a]pyrene; 7-OH-B[a]P, 7-hydroxy-benzo[a]pyrene; 9-OH-B[a]P, 9-hydroxy-benzo[a]pyrene; PGE2, prostaglandin E2; UGT, UDP-glucuronosyltransferases
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Introduction |
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Exposure to polycyclic aromatic hydrocarbons is an important cause of cancer because these molecules are activated by selected enzymes, including P-450 s and cyclooxygenase (COX) to carcinogenic metabolites. For example, benzo[a]pyrene (B[a]P), a component of tobacco smoke, undergoes metabolic biotransformation to electrophilic intermediates that react with cellular DNA and protein. The extent to which a given exposure to carcinogens produces adducts between reactive metabolites and cellular components in vivo depends on the balance between rates of oxidation of the parent compound and rates of detoxification of reactive metabolites via conjugation (1). Thus, induction of mono-oxygenase enzymes (2) or inhibition of conjugating enzymes (1,3) enhances the covalent binding of B[a]P metabolites to DNA.
The cytochrome P-450 family of enzymes including CYP1A1 and CYP1B1 is widely recognized for catalyzing oxidative reactions and activating xenobiotics to reactive metabolites that
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Materials and methods |
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Materials
Preparation of 3-, 7- and 9-OH-B[a]P glucuronides
Cell culture
PGE2 production
Western blotting
Northern blotting
Plasmids
Transient transfection assays
Patient samples
Analysis of CYP1B1 expression
Statistics
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Results |
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Discussion |
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