Correlation of in vitro and in vivo growth suppression of MCF-7 human breast cancer by 2,3,7,8-tetrachlorodibenzo-p-dioxin

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 13; p. 3149
• Main Authors: Gierthy, J F, Bennett, J A, Bradley, L M, Cutler, D S
• Format: Journal Article
• Language: English
• Published: United States 01.07.1993
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Administration, Oral; Animals; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Division - drug effects; Disease Models, Animal; Environmental Exposure; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - pathology; Polychlorinated Dibenzodioxins - pharmacology; Stimulation, Chemical; Transplantation, Heterologous
• ISSN: 0008-5472

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.