Estrogenic and thyroid hormone activity of a series of hydroxy-polychlorinated biphenyls.
A series of novel synthetic monohydroxy polychlorinated biphenyls (OH-PCBs) (5 trichloro-, 5 tetrachloro- and 5 pentachloro-compounds) have been characterized (1H and 13C NMR and high resolution MS) and their estrogenic and thyroid hormone activities assessed using a yeast two-hybrid assay, both with and without possible metabolic activation by rat liver S9 preparation. Moderate estrogenic activity was found for 2,3,4(')-trichlorobiphenyl-4-ol (compound 5) but this was eliminated when exposed to the S9 mix. 2,2('),3('),4,6-Pentachlorobiphenyl-3-ol (13) and 2('),3,3('),6-tetrachlorobiphenyl-4-ol (10) both showed weak estrogenicity in the absence of the S9 mix. The estrogenicity of compound (10) was enhanced 10-fold by exposure to S9 metabolic activation but that of compound (13) remained unchanged. 2('),4,5('),6-Tetrachlorobiphenyl-2-ol (6) showed strong thyroid hormonal activity (5% of that of T4) whereas 3('),4,6-trichlorobiphenyl-3-ol (4), compound (10) and 2,3('),4,5('),6-pentachlorobiphenyl-3-ol (14) showed moderate activity, and 2('),3,3('),5-tetrachlorobiphenyl-2-ol (8) and 3,3('),5,5('),6-pentachlorobiphenyl-2-ol (11) showed weak activity. The activity of (4) was eliminated by S9 metabolic activation whereas those of (6) and (14) were weakened and that of (10) remained unchanged.
Shiraishi
F
F
National Institute for Environmental Studies, Endocrine Disrupter Research Laboratory, 16-2 Onogawa, Tsukuba, 305-8506, Ibaraki, Japan.
Okumura
T
T
Nomachi
M
M
Serizawa
S
S
Nishikawa
J
J
Edmonds
J S
JS
Shiraishi
H
H
Morita
M
M
D001681:Biological Assay; D004785:Environmental Pollutants / Q000009:adverse effects*; D009682:Magnetic Resonance Spectroscopy; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D013974:Thyroxine / Q000187:drug effects* / Q000494:pharmacology*; D015003:Yeasts
D004785:Environmental Pollutants; D011960:Receptors, Estrogen; D011078:Polychlorinated Biphenyls; D013974:Thyroxine