Effects of the beta-isomer of hexachlorocyclohexane on estrogen-sensitive human mammary tumor cells.
The effects of the beta-isomer of hexachlorocyclohexane (beta-HCH) on the induction of the cytosolic progesterone receptor (PgRc), on the redistribution of the estrogen receptor (ER), and its affinity for ER were investigated in the estrogen-sensitive human mammary tumor cell line MCF-7. The effects of beta-HCH were compared to those of estradiol-17 beta (E2) and 2,4,6-trichlorophenol (TCP), a major urinary metabolite of beta-HCH in rats. beta-HCH in concentrations higher than 1 microM caused induction of PgRc whereas TCP was essentially without effect up to a cytotoxic concentration of 100 microM. Furthermore, beta-HCH (10 microM) caused redistribution of ER, i.e., decrease of cytosolic ER concentration and increase of nuclear ER concentration, in a way similar to E2. In contrast to this, beta-HCH up to a molar excess of 6 X 10(4) (concentration 30 microM) caused no significant displacement of [3H]E2 from ER indicating that beta-HCH has no substantial affinity for ER. It is concluded that beta-HCH has estrogenic properties which are at variance with the failure to demonstrate binding of beta-HCH to ER.
Coosen
R
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Laboratory of Toxicology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
van Velsen
F L
FL
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001943:Breast Neoplasms / Q000032:analysis / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002733:Chlorophenols / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002733:Chlorophenols; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D001556:Hexachlorocyclohexane; C024564:2,4,6-trichlorophenol; C023888:beta-hexachlorocyclohexane