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IN VIVO RATE OF PHENOL GLUCURONIDATION BY RAINBOW TROUT
Citation:
Lien, G J., J Nichols*, A D. Hoffman, C. T. Jenson, AND J M. McKim. IN VIVO RATE OF PHENOL GLUCURONIDATION BY RAINBOW TROUT. Presented at Society of Toxicology National Meeting, San Francisco, CA, March 25-29, 2001.
Description:
Induction of vitellogenin (VTG) in male fish has become an accepted biomarker for xenoestrogenicity. This study utilized the male rainbow trout liver slice model to determine the estrogenicity of parent compound, methoxychlor (MXC) and metabolites, di-hydroxy methoxychlor (HPTE) and mono-hydroxy methoxychlor (MHMXC). Tissue slices were exposed to concentrations of MXC, HPTE or MHMXC for 72 h at 11 degrees C. VTG induction was assessed by measurement of VTG mRNA (Northern dot blot and RPA analysis) and VTG protein (ELISA). Slices exposed to estradiol were a positive control. There was significant induction at 72 h of both VTG mRNA and VTG protein in slices exposed to 10,000 nM HPTE). Exposure of slices to MHMXC resulted in no detectable induction of VTG mRNA or protein at the concentrations tested. Chemical concentrations wre measured in the exposure media at 0 and 72 h. HPTE or MHMXC were undetectable after 72 h, presumably due to rapid Phase II metabolic conjugation as seen with disappearance of E2 from initial exposure levels, detectable MXC was measured at 72 h. Thus, the rate of MXC metabolism in liver slices was significantly less than observed for E2, although adequate to support VTG induction. These results are contrasted with apparent lack of metabolic conversion of MXC to hydroxylated metabolites resulted in induction only upon exposure of cells to HPTE but not MXC. The ability of liver slices to metabolize MXC, presumably to HPTE prior to conjugation, is consistent with VTG induction noted in slices but not in the RTH-149 reporter gene assay where metabolism was absent. This demonstrates the utility of using a metabolically competent assay system to detect VTG induction as a consequence of biotransformation for screening of chemicals for potential endocrine disruption.