Hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone: interaction with thyroxine binding sites of rat thyroid hormone carriers ex vivo and in vitro.
Previous results have indicated that hexachlorobenzene (HCB)-induced hypothyroidism may be caused by its main metabolite pentachlorophenol (PCP), and by tetrachlorohydroquinone (TCHQ), rather than by the parent compound. In the present experiments it was investigated whether hormone displacement from serum carriers could be a factor in the development of this hypothyroidism. In an in vitro competition assay PCP was an effective competitor for the thyroxine (T4)-binding sites of serum carriers, whereas HCB was ineffective. Ex vivo experimental results demonstrated occupation of T4-binding sites in sera from PCP-exposed animals but not in sera from HCB- or TCHQ-treated animals. Competing ability for T4-binding sites was still present in sera of PCP-exposed animals but was absent in HCB- or TCHQ-exposed animals. The results suggest that thyroid hormone displacement by the major metabolite PCP may play a role in HCB-induced hypothyroidism.
van Raaij
J A
JA
TNO Medical Biological Laboratory, Rijswijk, The Netherlands.
van den Berg
K J
KJ
Notten
W R
WR
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006581:Hexachlorobenzene / Q000378:metabolism / Q000633:toxicity*; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D007037:Hypothyroidism / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D010416:Pentachlorophenol / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D013974:Thyroxine / Q000378:metabolism*
D006873:Hydroquinones; D006581:Hexachlorobenzene; C044578:2,3,5,6-tetrachlorohydroquinone; D010416:Pentachlorophenol; D013974:Thyroxine