Carcinogenesis, Vol 18, 1651-1654, Copyright © 1997 by Oxford University Press
EC Bonefeld Jorgensen, H Autrup and JC Hansen
Toxaphene (polychlorinated camphenes) is an insecticidal mixture of >670
chemicals, which was widely used until the mid 1980s. Due to their
lipophilic and volatile nature, these chemicals accumulate in animal and
human tissues and continue to be a major contaminant in marine and
freshwater biota. Cytotoxic and genotoxic effects in mammalian test systems
suggest that toxaphene is a carcinogen and reports support the hypothesis
that toxaphene could have tumor-promoting potential in human breast tissue.
In order to examine the potential of toxaphene as an environmental
endocrine disrupter, we investigated its effect on the estrogen receptor
(ER) function in human breast cancer MCF-7 cells. Using transient gene
expression experiments, we observed approximately 60% and 80% inhibition of
the constitutive and 17beta-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 interference of toxaphene with the ER
mediated responses was supported by a significant suppression of
endogenously expressed pS2 RNA and decreased levels 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 disrupting activities which may affect
the reproductive health and increase the risk of carcinogenesis.
ARTICLES
Effect of toxaphene on estrogen receptor functions in human breast cancer cells
Department of Environmental and Occupational Medicine, University of Aarhus, Denmark.
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