ENVIRONMENTAL ESTROGEN STIMULATION OF GROWTH AND ESTROGEN RECEPTOR-FUNCTION IN PRENEOPLASTIC AND CANCEROUS HUMAN BREAST CELL-LINES

Background: DDT and polychlorinated biphenyls (PCBs), which are widesp read in the ecosystem, can mimic estrogen-mediated cell activities, Th us, they can potentially interfere with many physiologic processes, We compared the effects of organochlorines belonging to the DDT and PCB families, alone and in combination, for their ability to influence the estrogen receptor-mediated activities in preneoplastic breast epithel ial cells and breast cancer cells, Methods: Multiple assay systems req uiring functional estrogen receptor were employed to test estrogen-lik e activity of organochlorine ligands, Two-sided statistical tests were used to compare the data, Results: p,p'-DDT, the predominant form of DDT in the environment, is a more potent estrogen than o,p'-DDT (P<.00 1), although it is less effective than o,p'-DDT in inhibiting the bind ing of estradiol (natural estrogen) to estrogen receptor. Among the PC Bs, Heptachlor is estrogenic (in transient reporter assays; P less tha n or equal to.001), whereas Aroclor 1221 and Aroclor 1254, both indivi dually and in combination, are only weakly estrogenic, Conclusion: p,p '-DDT is the most effective organochlorine in regulating estrogen rece ptor-mediated cellular responses, In estrogen receptor-positive breast cancer cells, p,p'-DDT evokes responses by itself and enhances the re sponses in collaboration with estradiol or o,p'-DDT.