EFFECT OF TOXAPHENE ON ESTROGEN-RECEPTOR FUNCTIONS IN HUMAN BREAST-CANCER CELLS

Toxaphene (polychlorinated camphenes) is an insecticidal mixture of >6 70 chemicals, which was widely used until the mid 1980s. Due to their lipophilic and volatile nature, these chemicals accumulate in animal a nd human tissues and continue to be a major contaminant in marine and freshwater biota. Cytotoxic and genotoxic effects in mammalian test sy stems suggest that toxaphene is a carcinogen and reports support the h ypothesis that toxaphene could have tumor-promoting potential in human breast tissue. In order to examine the potential of toxaphene as an e nvironmental endocrine disrupter, we investigated its effect on the es trogen receptor (ER) function in human breast cancer MCF-7 cells, Usin g transient gene expression experiments, we observed similar to 60% an d 80% inhibition of the constitutive and 17 beta-estradiol induced ER- dependent transactivation, respectively, The involvement of the ER in the ability of toxaphene to block the estrogen action was verified by cotransfection studies in ER-negative MDA-MB-231 cells. The interferen ce of toxaphene with the ER mediated responses was supported by a sign ificant suppression of endogenously expressed pS2 RNA and decreased le vels of secreted pS2 protein, These reproducible results indicate that toxaphene can disturb hormonal signals mediated by the ER and suggest that these environmental chemicals have potential endocrine disruptin g activities which may affect the reproductive health and increase the risk of carcinogenesis.