Promotion of Endometriosis in Mice by Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls

Krista L. Johnson,¹ Audrey M. Cummings,² and Linda S. Birnbaum²

¹Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599-7270; ²U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Environmental Toxicology Division, Research Triangle Park, NC 27711

---

Abstract
Previous studies showed exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) enhances the development of endometriotic lesions. In this study we examined the effects of other polyhalogenated aromatic hydrocarbons on endometriotic proliferation. B6C3F₁ female mice were treated via oral gavage a total of five times, with 3 weeks between each dosing, with 0, 1, 3, or 10 µg 2,3,7,8-TCDD/kg body weight (bw); 3 or 30 mg 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153)/kg bw; 100, 300, or 1000 µg 3,3´,4,4´,5-pentachlorobiphenyl (PCB 126)/kg bw; 10, 30, or 100 µg 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF)/kg bw; or 2 or 20 mg 1,3,6,8-TCDD/kg at 10 ml/kg bw. Endometriosis was surgically induced during the week of the second dosing. Three weeks following the final dose, the mice were euthanized and endometriotic lesions, whole body, liver, ovaries, uterine horn, and thymus were weighed, and lesion diameters were measured. Lesions, uterine horns, and ovaries were fixed for histopathology and livers were processed for measurement of ethoxyresorufin O-deethylase (EROD) activity. Both 2,3,7,8-TCDD (1 and 3 µg/kg bw) and 4-PeCDF (100 µg/kg bw) significantly enhanced the growth of endometrial lesions. No statistically significant increase in endometriotic lesion size was detected in animals treated with either PCB 126 or with the highest dose of 2,3,7,8-TCDD, possibly due to the effects of histologically observed ovarian toxicity. The nondioxin-like compounds, PCB 153 and 1,3,6,8-TCDD, produced no observable effects on endometriosis. Hepatic EROD activity was significantly induced by 2,3,7,8-TCDD, 4-PeCDF, and PCB 126, but not by PCB 153 or 1,3,6,8-TCDD. The results of this study provide preliminary support for the hypothesis that halogenated aromatic hydrocarbon-promoted endometriosis may be Ah receptor mediated. Key words: endometriosis, halogenated aromatic hydrocarbon, polychlorinated biphenyls, polychlorinated dibenzofurans, polychlorinated dibenzo-p-dioxins, structure-activity relationships, TCDD. Environ Health Perspect 105:750-755 (1997)

---

Address correspondence to L.S. Birnbaum, U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Environmental Toxicology Division, MD-66, Room L-318, Research Triangle Park, NC 27711 USA.

The research described in this article has been funded in part by the U.S. Environmental Protection Agency with the University of North Carolina, Chapel Hill. The manuscript has been reviewed in accordance with EPA policy and approved for publication; however, it does not necessarily reflect the views of the agency. Mention of trade names or commercial products does not constitute endorsement or use recommendation.

The authors are grateful for the technical assistance of Michael DeVito, Janet Diliberto, Joan Metcalf, David Ross, Vicki Richardson, Joe Jackson, Frances McQuaid, Dennis House, Chris Hurst, and Michael Santostefano. In addition, the authors would like to thank Michael Santostefano, Barbara Abbott, and Michael DeVito for reviewing this manuscript.

Received 16 September 1996; accepted 2 April 1997.

---

[Table of Contents] [Full Article]

Last Update: July 23, 1997