In vitro assay for human thyroid hormone receptor β agonist and antagonist effects of individual polychlorinated naphthalenes and Halowax mixtures

Polychlorinated naphthalenes (PCNs) are dioxin-like environmental contaminants. There is growing concern over the endocrine-disrupting effects of PCNs, but very few studies have investigated the effect of PCNs on the thyroid system. This study used a yeast two-hybrid assay, which included the recombinant human thyroid receptor(TR)-β and reporter genes, to characterize the TRβ-disrupting effects of five individual PCN congeners, five PCN Halowax mixtures, and naphthalene. Their agonist and antagonist effects were studied in the absence and presence of 5×10-7 mol/L 3,3′,5-triiodo-L-thyronine, which induced submaximal β-galactosidase activity. Naphthalene, 1,2,3,4,5,6,7,8-octachloronaphthalene and all of the Halowax mixtures (Halowax 1000, 1001, 1013, 1014 and 1099) showed no agonist or antagonist activity on TRβ at the concentrations tested (up to 10-2 g/L). The lighter PCN congeners, namely 1-chloronaphthalene, 2-chloronaphthalene, 1,4-dichloronaphthalene and 1,2,3,4-tetrachloronaphthalene showed no agonist activity but showed significant antagonist activity on TRβ. The 20% relative inhibitory concentrations of these PCNs were less than 9.13 × 10-3 g/L. Thus, bioaccumulation of these lighter PCN congeners may disrupt the thyroid hormone system and inhibit TR-mediated cellular responses. Studies in the future should investigate the possible associations between the presence PCNs and adverse health outcomes.

Polychlorinated naphthalenes （PCNs） are dioxin-like environmental contaminants. There is growing concern over the endo- crine-disrupting effects of PCNs, but very few studies have investigated the effect of PCNs on the thyroid system. This study used a yeast two-hybrid assay, which included the recombinant human thyroid receptor（TR）-[3 and reporter genes, to characterize the TRy-disrupting effects of five individual PCN congeners, five PCN Halowax mixtures, and naphthalene. Their agonist and an- tagonist effects were studied in the absence and presence of 5×10-7 mol/L 3,3＇,5-triiodo-L-thyronine, which induced submaximal β-galactosidase activity. Naphthalene, 1,2,3,4,5,6,7,8-octachloronaphthalene and all of the Halowax mixtures （Halowax 1000, 1001, 1013, 1014 and 1099） showed no agonist or antagonist activity on TRI3 at the concentrations tested （up to 10-2 g/L）. The lighter PCN congeners, namely 1-chloronaphthalene, 2-chloronaphthalene, 1,4-dichloronaphthalene and 1,2,3,4-tetrachloronaph- thalene showed no agonist activity but showed significant antagonist activity on TRI3. The 20% relative inhibitory concentrations of these PCNs were less than 9.13 × 10-3 g/L. Thus, bioaccumulation of these lighter PCN congeners may disrupt the thyroid hormone system and inhibit TR-mediated cellular responses. Studies in the future should investigate the possible associations between the presence PCNs and adverse health outcomes.