Lack of synergy by mixtures of weakly estrogenic hydroxylated polychlorinated biphenyls and pesticides.
We examined the estrogenicity of binary mixtures of the hydroxylated polychlorinated biphenyls (OHPCBs) 2,4,6-trichloro-4'-biphenylol (2,4,6-TCB-4'-OH) and 2,3,4,5-tetrachloro-4'-biphenylol and the pesticides endosulfan and dieldrin. The OHPCBs and pesticides were tested in both the MCF-7 focus assay and a competitive estrogen-receptor binding assay. Although the individual OHPCBs were estrogenic in both assays, there was no synergy when they were combined at various concentrations as equimolar mixtures. Of the pesticides, only endosulfan was estrogenic. Its weak estrogenicity was seen only in the MCF-7 focus assay at the highest concentration tested--10 microM. There was no synergy of the equimolar mixture of pesticides. To determine whether OHPCBs might respond synergistically when combined with the natural estrogen 17-beta-estradiol (E2), we tested various concentrations of 2,4,6-TCB-4'-OH in the MCF-7 focus assay in combination with physiologically relevant concentrations of E2. There was no synergy between 2,4,6-TCB-4'-OH and E2. Pretreatment for 3 or 7 days with 2,4,6-TCB-4'-OH had no effect on subsequent foci induced by a concentration of 2,4,6-TCB-4'-OH and E2. Although our results showing no synergy between the pesticides or the OHPCBs are in contrast to a recent report that binary mixtures of these same compounds produce synergistic responses in estrogen-sensitive assays, they are in agreement with the results from other assays showing a lack of synergy. Considering all results, it appears that synergy of these weakly estrogenic compounds acting through the estrogen receptor is unlikely.
School of Public Health, State University of New York at Albany, USA.
K F
KF
Arcaro
D D
DD
Vakharia
Y
Y
Yang
J F
JF
Gierthy
D000230:Adenocarcinoma; D001667:Binding, Competitive; D001943:Breast Neoplasms; D004026:Dieldrin / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004726:Endosulfan / Q000009:adverse effects / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D007306:Insecticides / Q000009:adverse effects / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000009:adverse effects / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004967:Estrogens; D007306:Insecticides; D011960:Receptors, Estrogen; D011078:Polychlorinated Biphenyls; D004026:Dieldrin; D004726:Endosulfan