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Metabolic Activation of Nonpolar Sediment Extracts Results in Enhanced Thyroid Hormone Disrupting Potency
journal contribution
posted on 2013-08-06, 00:00 authored by Mauricio Montaño, Jana Weiss, Lucien Hoffmann, Arno Christian Gutleb, AlberTinka
Jacoba MurkTraditional sediment
risk assessment predominantly considers the
hazard derived from legacy contaminants that are present in nonpolar
sediment extracts, such as polychlorinated biphenyls (PCBs), dioxins,
furans (PCDD/Fs), and polyaromatic hydrocarbons (PAHs). Although in
vivo experiments with these compounds have shown to be thyroid hormone
disrupting (THD), in vitro their THD potency is not observed in nonpolar
sediment extracts. This is hypothesized to be due to the absence of
in vitro biotransformation which will result in bioactivation of the
lipophilic compounds into THD hydroxyl metabolites. This study reveals
that indeed metabolically activated nonpolar contaminants in sediments
can competitively bind to thyroid hormone transport proteins. Sediment
fractions were incubated with S9 rat microsomes, and the metabolites
were extracted with a newly developed method that excludes most of
the lipids to avoid interference in the applied nonradioactive 96-well
plate TTR competitive binding assay. Metabolic activation increased
the TTR binding potency of nonpolar fractions of POP-polluted sediments
up to 100 times, resulting in potencies up to 240 nmol T4 equivalents/g sediment equivalent (nmol T4-Eq/g SEQ).
This demonstrates that a more realistic in vitro sediment THD risk
characterization should also include testing of both polar and medium
polar sediment extracts for THD, as well as bioactivated nonpolar
sediment fractions to prevent underestimation of its toxic potency.
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Keywords
PAHnonpolar contaminantsbinding assaypolyaromatic hydrocarbons100 timesTHD potencynonpolar sediment extractssediment THD risk characterizationlegacy contaminantsnonpolar fractionsplate TTRlipophilic compoundsSEQTTR binding potencyPCDDsediment extractsthyroid hormoneSediment fractionsMetabolic Activationthyroid hormone transport proteinsvivo experimentsNonpolar Sediment Extracts ResultsTHD hydroxyl metabolitesbioactivated nonpolar sediment fractionsS 9 rat microsomesMetabolic activationEnhanced Thyroid Hormone Disrupting PotencyTraditional sediment risk assessmentpolychlorinated biphenyls
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