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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
|
| pubmed:dateCreated |
1993-7-30
|
| pubmed:abstractText |
The purpose of this study was to compare the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the in vitro and in vivo 17 beta-estradiol (E2)-dependent growth of MCF-7 human breast cancer cells. In culture, a major component of postconfluent growth of MCF-7 cells is E2 dependent. In vivo, MCF-7 cells fail to grow as xenografts without exogenous E2 support. Thus the effect of TCDD on postconfluent MCF-7 growth in culture was compared with its effect on MCF-7 xenograft growth in immunosuppressed mice. A concentration of 10(-9) M E2 was optimal for supporting postconfluent growth of MCF-7 cells in culture into multicellular aggregates (foci) on a monolayer background. The 50% inhibitory dose of TCDD under these conditions was 3 x 10(-10) M, while E2-dependent focus development was completely inhibited by 10(-8) M TCDD. Weekly i.p. administration of TCDD (5 micrograms/kg) to mice bearing MCF-7 tumor xenografts resulted in inhibition of the tumor growth rate for the first 2 weeks, followed by recovery to the control growth rate during the third week. These recovered tumors were found to retain estrogen-dependent growth as shown by second generation transplantation studies. The p.o. route of TCDD administration yielded a similar 2-week transient suppression of growth with a concentration of 8 micrograms TCDD/kg body weight but only a 1-week growth rate latency with a 2-microgram/kg body weight dose. A single 5-micrograms/kg dose given 1 day after implantation was virtually noninhibitory. These results indicate that TCDD suppression of estrogen-dependent MCF-7 human breast cancer cell growth in vitro was predicative of a similar growth suppression of MCF-7 solid tumor xenografts in vivo. However, additional host-related factors must be involved in vivo, since suppression of tumor growth is transient. These studies provide a basis for future in vivo investigations of TCDD endocrine toxicity by using the MCF-7 tumor as a surrogate estrogen-responsive human organ and to examine the efficacy of TCDD and related Ah receptor-mediated compounds in the management of human estrogen-dependent breast cancer.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
53
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3149-53
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8319224-Adenocarcinoma,
pubmed-meshheading:8319224-Administration, Oral,
pubmed-meshheading:8319224-Animals,
pubmed-meshheading:8319224-Breast Neoplasms,
pubmed-meshheading:8319224-Cell Division,
pubmed-meshheading:8319224-Disease Models, Animal,
pubmed-meshheading:8319224-Environmental Exposure,
pubmed-meshheading:8319224-Estradiol,
pubmed-meshheading:8319224-Estrogen Antagonists,
pubmed-meshheading:8319224-Female,
pubmed-meshheading:8319224-Humans,
pubmed-meshheading:8319224-Male,
pubmed-meshheading:8319224-Mice,
pubmed-meshheading:8319224-Mice, Inbred C57BL,
pubmed-meshheading:8319224-Mice, Inbred DBA,
pubmed-meshheading:8319224-Neoplasms, Hormone-Dependent,
pubmed-meshheading:8319224-Stimulation, Chemical,
pubmed-meshheading:8319224-Tetrachlorodibenzodioxin,
pubmed-meshheading:8319224-Transplantation, Heterologous
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Correlation of in vitro and in vivo growth suppression of MCF-7 human breast cancer by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
|
| pubmed:affiliation |
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
|