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Metabolism of benzo[a]pyrene and persistence of DNA adducts in the brown bullhead (Ictalurus nebulosus)
Institution:1. Division of Environmental Toxicology and Chemistry, Center for Environmental Research, State University of New York College at Buffalo, Buffalo, NY 14222, U.S.A.;4. Department of Preventive Medicine and Environmental Health, University of Kentucky Medical Center, Lexington, KY 40536, U.S.A.;1. Mayo Clinic Alix School of Medicine, Scottsdale, Mayo Clinic, AZ;2. Department of Emergency Medicine, Mayo Clinic, Rochester, MN;3. Department of Emergency Medicine, Mayo Clinic, Phoenix, AZ;1. Institute of Engineering, Academic Assembly, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan;2. Shinshu University, Japan;1. Institute of Chemistry and Chemical Technology, Mongolian Academy of Sciences, Ulaanbaatar 13330, Mongolia;2. State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001, PR China;3. University of Chinese Academy of Sciences, Beijing 100049, PR China;1. Universitat de Valéncia, Spain;2. Universitat Jaume I and Ivie, Spain
Abstract:
  • 1.1. The in vitro metabolism of 3H]benzoa]pyrene (BP) and 14C]benzoa]pyrene-7,8-dihydrodiol (BP-7,8-diol) by liver of brown bullhead (Ictalurus nebulosus) was characterized, as was the formation and persistence of BP-DNA adducts in vivo.
  • 2.2. Compared to rat liver microsomes, bullhead liver microsomes produced relatively larger amounts of BP-7,8-diol (predominantly the ?] enantiomer) and smaller amounts of BP-4,5-diol.
  • 3.3. BP phase I metabolites were efficiently converted by freshly isolated bullhead hepatocytes to conjugates, predominantly glucuronides.
  • 4.4. BP-7,8-diol was metabolized by hepatocytes 4-fold more rapidly than was BP and was converted to approximately equal amounts of glucuronides, glutathione conjugates and sulfates.
  • 5.5. BP-DNA adducts formed in bullhead liver with a lag time of several days and maximum adduct formation at 25–30 days. The major adduct was anti-BPDE-deoxyguanosine.
Keywords:
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