Effect of toxaphene on estrogen receptor functions in human breast cancer cells

Toxaphene (polychlorinated camphenes) is an insecticidal mixture of >670chemicals, which was widely used until the mid 1980s. Due to theirlipophilic and volatile nature, these chemicals accumulate in animal andhuman tissues and continue to be a major contaminant in marine andfreshwater biota. Cytotoxic and genotoxic effects in mammalian test systemssuggest that toxaphene is a carcinogen and reports support the hypothesisthat toxaphene could have tumor-promoting potential in human breast tissue.In order to examine the potential of toxaphene as an environmentalendocrine disrupter, we investigated its effect on the estrogen receptor(ER) function in human breast cancer MCF-7 cells. Using transient geneexpression experiments, we observed approximately 60% and 80% inhibition ofthe constitutive and 17beta-estradiol induced ER-dependent transactivation,respectively. The involvement of the ER in the ability of toxaphene toblock the estrogen action was verified by cotransfection studies inER-negative MDA-MB-231 cells. The interference of toxaphene with the ERmediated responses was supported by a significant suppression ofendogenously expressed pS2 RNA and decreased levels of secreted pS2protein. These reproducible results indicate that toxaphene can disturbhormonal signals mediated by the ER and suggest that these environmentalchemicals have potential endocrine disrupting activities which may affectthe reproductive health and increase the risk of carcinogenesis.