TY - JOUR
T1 - Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity
AU - Bonefeld-Jørgensen, E.C.
AU - Andersen, H. R.
AU - Rasmussen, T.H.
AU - Vinggaard, Anne
PY - 2001
Y1 - 2001
N2 - Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we present evidence that the three PCBs most abundant in biological extracts, 2,2',3'4,4',5-hexachlorobiphenyl (PCB # 138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB # 153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB # 180) have pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17 beta -Estradiol. whereas the compounds inhibited cell growth significantly at 1 and 10 muM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17 beta -estradiol induced MCF-7 cells. In addition, PCB # 138 elicited a dose-dependent antagonistic effect on androgen receptor activity in transiently co-transfected Chinese Hamster Ovary cells with an IC50, of 6.2 muM. In summary, this study indicate that the di-ortho, multiple-chloro substituted biphenyls, PCB # 138, PCB # 153 and PCB # 180, can compete with the binding of the natural ligand to two nuclear receptors and thus possess the ability to interfere with sexual hormone regulated processes.
AB - Polychlorinated biphenyls (PCBs) are ubiquitous environmental persistent contaminants giving rise to potential health hazard. Some PCBs exert dioxin-like activities mediated through the aryl hydrocarbon receptor. Although reports on interaction with other nuclear receptors are sparce, some congeners are hypothesized to possess endocrine disruptive potential. Here we present evidence that the three PCBs most abundant in biological extracts, 2,2',3'4,4',5-hexachlorobiphenyl (PCB # 138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB # 153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB # 180) have pleiotropic effects on the estrogen- and androgen-receptor. In MCF-7 cells a slightly increased cell proliferation was observed at low concentrations (1-10 nM) in cells co-treated with 0.01 nM 17 beta -Estradiol. whereas the compounds inhibited cell growth significantly at 1 and 10 muM. In reporter gene (ERE-tk-CAT) analysis the three congeners exhibited a significantly estrogen receptor-ligand mediated decrease of the chloramphenicol transferase activity in both control and 10 nM 17 beta -estradiol induced MCF-7 cells. In addition, PCB # 138 elicited a dose-dependent antagonistic effect on androgen receptor activity in transiently co-transfected Chinese Hamster Ovary cells with an IC50, of 6.2 muM. In summary, this study indicate that the di-ortho, multiple-chloro substituted biphenyls, PCB # 138, PCB # 153 and PCB # 180, can compete with the binding of the natural ligand to two nuclear receptors and thus possess the ability to interfere with sexual hormone regulated processes.
KW - AH-receptor
KW - androgen receptor
KW - breast cancer cells
KW - TCDD
KW - PCB
KW - estrogen receptor
U2 - 10.1016/S0300-483X(00)00368-1
DO - 10.1016/S0300-483X(00)00368-1
M3 - Journal article
VL - 158
SP - 141
EP - 153
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 3
ER -