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Title: Mechanisms of fenthion activation in rainbow trout (Oncorhynchus mykiss) acclimated to hypersaline environments

Previous studies in rainbow trout have shown that acclimation to hypersaline environments enhances the toxicity to thioether organophosphate and carbamate pesticides. In order to determine the role of biotransformation in this process, the metabolism of the thioether organophosphate biocide, fenthion was evaluated in microsomes from gills, liver and olfactory tissues in rainbow trout (Oncorhynchus mykiss) acclimated to freshwater and 17 per mille salinity. Hypersalinity acclimation increased the formation of fenoxon and fenoxon sulfoxide from fenthion in liver microsomes from rainbow trout, but not in gills or in olfactory tissues. NADPH-dependent and independent hydrolysis was observed in all tissues, but only NADPH-dependent fenthion cleavage was differentially modulated by hypersalinity in liver (inhibited) and gills (induced). Enantiomers of fenthion sulfoxide (65% and 35% R- and S-fenthion sulfoxide, respectively) were formed in liver and gills. The predominant pathway of fenthion activation in freshwater appears to be initiated through initial formation of fenoxon which may be subsequently converted to the most toxic metabolite fenoxon R-sulfoxide. However, in hypersaline conditions both fenoxon and fenthion sulfoxide formation may precede fenoxon sulfoxide formation. Stereochemical evaluation of sulfoxide formation, cytochrome P450 inhibition studies with ketoconazole and immunoblots indicated that CYP3A27 was primarily involved in the enhancement of fenthionmore » activation in hypersaline-acclimated fish with limited contribution of FMO to initial sulfoxidation.« less
Authors:
 [1] ;  [2] ;  [3]
  1. Department of Environmental Chemistry, University of California Riverside, 900 University Ave., Riverside, CA 92521 (United States), E-mail: lavado.ramon@ucr.edu
  2. Department of Medicinal Chemistry and Environmental Toxicology, University of Mississippi, MS 38677 (United States)
  3. Department of Environmental Chemistry, University of California Riverside, 900 University Ave., Riverside, CA 92521 (United States)
Publication Date:
OSTI Identifier:
21182741
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 235; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2008.11.017; PII: S0041-008X(08)00498-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL ADAPTATION; CARBAMATES; CLEAVAGE; EVALUATION; FRESH WATER; GILLS; HYDROLYSIS; INHIBITION; LIVER; METABOLISM; MICROSOMES; PESTICIDES; SALINITY; STEREOCHEMISTRY; SULFOXIDES; TOXICITY; TROUT