Enhancement of 2- and 16 alpha-estradiol hydroxylation in MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-P-dioxin.
2,3,7,8-Tetrachlorodibenzo-p-dioxin exhibits antiestrogenic activity and induces cytochromes P-450 in estrogen-dependent MCF-7 human breast-cancer cells. To determine whether induction of 2- or 16 alpha-hydroxylation of 17 beta-estradiol has a role in this antiestrogenic activity, MCF-7 cells which were exposed to this xenobiotic for 72 hrs were incubated with either [2-3H] or [16 alpha-3H] 17 beta-estradiol and the extent of tritiated H2O formation, indicative of site-specific hydroxylation, was determined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-treated MCF-7 cultures showed an 8-fold increase in 2-hydroxylation and a 2-fold increase in 16 alpha-hydroxylation. These results support the suggestion that increased hydroxylation of 17 beta-estradiol may have a role in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells.
Gierthy
J F
JF
Wadsworth Center for Laboratories & Research, New York State Department of Health, Albany 12201-0509.
Lincoln
D W
DW
Kampcik
S J
SJ
Dickerman
H W
HW
Bradlow
H L
HL
Niwa
T
T
Swaneck
G E
GE
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004147:Dioxins / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D039181:Steroid 16-alpha-Hydroxylase; D014407:Tumor Cells, Cultured
D004147:Dioxins; D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase