Pvm. Shekhar et al., ENVIRONMENTAL ESTROGEN STIMULATION OF GROWTH AND ESTROGEN RECEPTOR-FUNCTION IN PRENEOPLASTIC AND CANCEROUS HUMAN BREAST CELL-LINES, Journal of the National Cancer Institute, 89(23), 1997, pp. 1774-1782
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.