In vitro estrogenicity of the catechol metabolites of selected polychlorinated biphenyls

A considerable body of work has demonstrated that phenolic polychlorinated biphenyl (PCB) metabolites, structural analogues to estradiol, bind to the soluble estrogen receptor (ER) and that hydroxy PCB-ER complexes will trans locate into the nucleus and bind to ER response elements in cultured cells. Although catechol estrogens exhibit weak estrogenic activity, the catechol PCB metabolites which are structurally similar to these ER agonists have g one untested for potential estrogenicity, In the present work we have asses sed the estrogenicity of this second group of PCB metabolites, the catechol s. The test compounds used in the present study were chosen to elucidate th e effects of chlorine and catechol position on in vitro estrogenicity, Cult ured HeLa cells, transfected with the estrogen reporter gene ERET81CAT and mouse ER cDNA, were incubated with PCB catechols. The cells were harvested at 28 h posttransfection and assayed for chloramphenicol acetyl transferase (CAT) activity. The responses elicited by the PCB catechols tested fell wi thin the range of effect measured for the catechol estrogens and phenolic P CBs, and were within the range previously reported for other "environmental estrogens" such as nonylphenol and o,p'-DDT. Maximal measured responses we re achieved at concentrations approximately two to three orders of magnitud e higher than that of 17-beta-estradiol, indicating that PCB catechols have estrogenic activity in vitro. The extent of chlorination and the position of the catechol (3,4 vs 2,3 substitution) were important in determining est rogenicity in the compounds tested. The 2,3-catechol showed no detectable a ctivity in this system, while activity of the 3,4-catechols increased with the degree of chlorination. The observed estrogenicity of PCB catechols sug gests that further oxidative metabolism of estrogenic PCB phenolic metaboli tes would not necessarily result in lowering the total estrogenic burden of a PCB-exposed organism. The present results imply that if estrogenic activ ity is assigned to an individual phenol, the potential contribution of its catechol metabolites to the total estrogenic burden should also be taken in to consideration.