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 ...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.展开更多
基金supported by the National Basic Research Program of China (2009CB421605)the National Natural Science Foundation of China (20877089 and 20737003)
文摘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.
