Antiestrogenic potentials of ortho-PCB congeners by single or complex exposure.
Di-ortho PCB congeners 52, 138, 153 and 180, and the mono-ortho coplanar congener 118 have been detected as a complex mixture in human tissue in Korea. This study examined the antiestrogenic effects of samples exposed to single or combination treatment of the ortho-PCB congeners. In order to determined the combined toxicity, a sample mixture (M1, M2, M3, M4, and M5) was designed based on the ortho-PCB congeners found in Korean human tissue. With the exception of PCB 52, the ortho-PCB congeners (PCB 118, 138, 153, and 180) showed weak antiestrogenic activity. The antiestrogenic activity of di-ortho PCB congeners (PCB 138, 153, and 180) was induced by the depletion of endogenous E2 as well as through the ER-dependent pathway, whereas the antiestrogenic activity of mono-ortho PCB 118 was only induced through the depletion of endogenous E2. When the MCF7-BUS cells were treated with mixtures containing the no effective concentration (10(-6) M) of the PCB congeners, M3 (PCB 118 + PCB 138 + PCB 180) and M4 (PCB 118 + PCB 138) had an antiestrogenic effect but the other mixtures (M1; PCB 52 + PCB 118 + PCB 138 + PCB 180, M2; PCB 118 + PCB 138 + PCB 153 + PCB 180, M5; PCB 118 + PCB 180) did not. Although the mechanism for the interaction between the PCB congeners is not completely understood, it was presumed that exposure to a mixture of the PCB congeners might have synergistic effects on their antiestrogenicity through the ER-independent pathway.
Oh
Seung Min
SM
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Ryu
Byung Taek
BT
Lee
Sang Ki
SK
Chung
Kyu Hyuck
KH
D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000737:chemistry / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection; D014819:Vitellogenins / Q000235:genetics
D045424:Complex Mixtures; D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D014819:Vitellogenins; D011078:Polychlorinated Biphenyls; D008156:Luciferases; D001141:Aromatase; D019363:Cytochrome P-450 CYP1A1