PMID- 22859314
OWN - NLM
STAT- MEDLINE
DCOM- 20130327
LR  - 20161125
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 130
IP  - 1
DP  - 2012 Nov
TI  - New approaches to assess the transthyretin binding capacity of bioactivated 
      thyroid hormone disruptors.
PG  - 94-105
LID - 10.1093/toxsci/kfs228 [doi]
AB  - Polychlorinated biphenyls (PCBs) and polybrominated diphenyl-ethers (PBDEs) are 
      metabolized into hydroxylated metabolites (OH-PCBs/PBDEs), which can disrupt the 
      thyroid hormone homeostasis. Binding of these metabolites to transport proteins 
      such as transthyretin (TTR) is an important mechanism of their toxicity. Several 
      methods to quantify the competitive thyroxine (T(4)) displacement potency of pure 
      metabolites exist. However, quantification of the potency of in vitro metabolized 
      PCBs and PBDEs has drawbacks related to the coextraction of compounds disturbing 
      the T(4)-TTR competitive binding assay. This study identifies and quantifies the 
      major coextractants namely cholesterol, saturated and nonsaturated fatty acids 
      (SFA and NSFA) at levels above 20 nmol per mg equivalent protein following 
      various extraction methods. Their TTR binding potency was analyzed in a 
      downscaled, nonradioactive fluorescence displacement assay. At concentration 
      factors needed for TTR competitive binding, at least 10muM of these coextracts is 
      present, whereas individual SFA and NSFA disturb the assay from 0.3muM. The 
      effectiveness of the in vitro metabolism and extraction of the model compounds CB 
      77 and BDE 47 was chemically quantified with a newly developed chromatographic 
      method analyzing silylated derivatives of the OH-metabolites and coextractants. A 
      new method to selectively extract metabolites and limit coextraction of 
      disturbing compounds to less than 5 nmol per mg equivalent protein is presented. 
      It is now possible to make a dose-response curve up to 50% inhibition with 
      bioactivated CB 77 and BDE 47. The toxic potencies of bioactivated persistent 
      organic pollutants (POPs) should be taken into account to prevent serious 
      underestimation of their hazard and risk.
FAU - Montano, Mauricio
AU  - Montano M
AD  - Centre de Recherche Public - Gabriel Lippmann, Department Environment and 
      Agro-biotechnologies, L-4422 Belvaux, Grand Duchy of Luxembourg.
FAU - Cocco, Emmanuelle
AU  - Cocco E
FAU - Guignard, Cedric
AU  - Guignard C
FAU - Marsh, Goran
AU  - Marsh G
FAU - Hoffmann, Lucien
AU  - Hoffmann L
FAU - Bergman, Ake
AU  - Bergman A
FAU - Gutleb, Arno Christian
AU  - Gutleb AC
FAU - Murk, Albertinka Jacoba
AU  - Murk AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120801
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Fatty Acids)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Halogenated Diphenyl Ethers)
RN  - 0 (Polybrominated Biphenyls)
RN  - 0 (Prealbumin)
RN  - 0N97R5X10X (2,2',4,4'-tetrabromodiphenyl ether)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - Q51BO43MG4 (Thyroxine)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - Cholesterol/chemistry/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Endocrine Disruptors/*metabolism
MH  - Environmental Pollutants/chemistry/*metabolism
MH  - Fatty Acids/chemistry/metabolism
MH  - Fatty Acids, Unsaturated/chemistry/metabolism
MH  - Halogenated Diphenyl Ethers
MH  - Microsomes, Liver/drug effects/metabolism
MH  - Polybrominated Biphenyls/chemistry/*metabolism
MH  - Polychlorinated Biphenyls/chemistry/*metabolism
MH  - Prealbumin/*metabolism
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thyroxine/*metabolism
EDAT- 2012/08/04 06:00
MHDA- 2013/03/28 06:00
CRDT- 2012/08/04 06:00
PHST- 2012/08/04 06:00 [entrez]
PHST- 2012/08/04 06:00 [pubmed]
PHST- 2013/03/28 06:00 [medline]
AID - kfs228 [pii]
AID - 10.1093/toxsci/kfs228 [doi]
PST - ppublish
SO  - Toxicol Sci. 2012 Nov;130(1):94-105. doi: 10.1093/toxsci/kfs228. Epub 2012 Aug 1.