Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout
- Oregon State University, Department of Environmental and Molecular Toxicology, Corvallis, OR (United States)
- National Marine Fisheries Service, Northwest Fisheries Science Center, Newport, OR (United States)
- National Marine Fisheries Service, Northwest Fisheries Science Center, Seattle, WA (United States)
- Woods Hole Oceanographic Institution, Department of Biology, Woods Hole, MA (United States)
This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100 nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2 nM [{sup 3}H]2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin from rainbow trout AHR2{alpha}. Based on appearance of fluorescent aromatic compounds in bile over 3, 7, 14, 28 or 50 days of feeding 3 {mu}g of BaP or BeP/g fish/day, rainbow trout liver readily excreted these polyaromatic hydrocarbons (PAHs) and their metabolites at near steady state rates. CYP1A proteins catalyzed more than 98% of ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout hepatic microsomes. EROD activity of hepatic microsomes initially increased and then decreased to control activities after 50 days of feeding both PAHs. Immunohistochemistry of liver confirmed CYP1A protein increased in fish fed both PAHs after 3 days and remained elevated for up to 28 days. Neither BaP nor BeP increased hepatic DNA adduct concentrations at any time up to 50 days of feeding these PAHs. Comet assays of blood cells demonstrated marked DNA damage after 14 days of feeding both PAHs that was not significant after 50 days. There was a strong positive correlation between hepatic EROD activity and DNA damage in blood cells over time for both PAHs. Neither CYP1A protein nor 3-nitrotyrosine (a biomarker for oxidative stress) immunostaining in trunk kidney were significantly altered by BaP or BeP after 3, 7, 14, or 28 days. There was no clear association between AHR2{alpha} affinity and BaP and BeP-induced oxidative stress. - Highlights: > No direct association between aryl hydrocarbon receptor affinity and polyaromatic hydrocarbon induced oxidative stress. > There was a strong correlation between cytochrome P4501A activity and oxidative stress as measured with the comet assay. > There was no correlation between cytochrome P4501A protein and oxidative stress as measured with the comet assay.
- OSTI ID:
- 21587774
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 254, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.04.015; PII: S0041-008X(11)00154-2; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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AFFINITY
BLOOD CELLS
DNA ADDUCTS
DNA DAMAGES
EXCRETION
FEEDING
FLUORESCENCE
KIDNEYS
LIVER
MICROSOMES
OXIDATION
POLYCYCLIC AROMATIC HYDROCARBONS
PYRENE
RECEPTORS
STRESSES
TROUT
ADDUCTS
ANIMALS
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AROMATICS
BIOLOGICAL MATERIALS
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BODY FLUIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CLEARANCE
CONDENSED AROMATICS
DIGESTIVE SYSTEM
EMISSION
FISHES
GLANDS
HYDROCARBONS
LUMINESCENCE
MATERIALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PHOTON EMISSION
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VERTEBRATES