2,3,7,8-Tetrachlorodibenzo-p-dioxin causes an extensive alteration of 17. beta. -estradiol metabolism in MCF-7 breast tumor cells

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.17.6917· OSTI ID:5464399

Spink, D C; Lincoln, II, D W; Dickerman, H W; Gierthy, J F ^[1]

---

1. New York State Dept. of Health, Albany (USA)

MCF-7 breast tumor cells form multicellular foci in vitro when supplemented with 17{beta}-estradiol (E{sub 2}). In the presence of E{sub 2} and the aryl hydrocarbon-receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), MCF-7 cells grow to confluence but do not form foci. To investigate the role of E{sub 2} metabolism in this antiestrogenic effect of TCDD, analyses were performed by capillary GC/MS. The results revealed the pretreatment of MCF-7 cultures with TCDD (10 nM) rapidly depletes E{sub 2}. In untreated cultures supplemented with 10 nM E{sub 2}, the concentration of free E{sub 2} decreased to 4 nM in the first 12 hr, followed by a slower rate of decline. After 3 days most E{sub 2} in the medium was in conjugated form(s); 1.7 nM was present as free E{sub 2}, and 2.9 nM was released by treatment with glucuronidas/sulfatase. In TCDD-treated cultures, E{sub 2} declined to 290 pM in 12 hr and after 2 days was not detected (<100 pM) either as free steroid or after treatment with glucuronidas/sulfatas. Intracellular E{sub 2} and estrone were likewise depleted by pretreatment with TCDD. Microsomes from TCDD-treated cells showed highly elevated aryl hydrocarbon-hydroxylase activity and catalyzed hydroxylations of E{sub 2} at C-2, C-4, C-15{alpha}, and C-6{alpha} with a combined rate of 0.85 nmol/min per nmol of cytochrome P-450 at saturating E{sub 2}. These results suggest that depletion of E{sub 2} by enhanced metabolism accounts for the antiestrogenic activity of TCDD in MCF-7 cells.

• OSTI ID: 5464399
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:17; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHLORINATED AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
ESTRADIOL
METABOLISM
DEUTERIUM COMPOUNDS
DIOXIN
GAS CHROMATOGRAPHY
HYDROXYLASES
HYDROXYLATION
MAMMARY GLANDS
MASS SPECTROSCOPY
RECEPTORS
TUMOR CELLS
ANIMAL CELLS
AROMATICS
BODY
CHROMATOGRAPHY
ENZYMES
ESTRANES
ESTROGENS
GLANDS
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
MEMBRANE PROTEINS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PROTEINS
SEPARATION PROCESSES
SPECTROSCOPY
STEROID HORMONES
STEROIDS
550201* - Biochemistry- Tracer Techniques