Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls.
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 micrograms 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 micrograms 3,3',4,4',5-pentachlorobiphenyl (PCB 126)/kg bw; 10, 30, or 100 micrograms 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 weighted, 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 micrograms/kg bw) and 4-PeCDF (100 micrograms/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.
Johnson
K L
KL
University of North Carolina, Chapel Hill 27599-7270, USA.
Cummings
A M
AM
Birnbaum
L S
LS
D000818:Animals; D001572:Benzofurans / Q000009:adverse effects / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D006846:Hydrocarbons, Halogenated / Q000009:adverse effects / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D051379:Mice; D010053:Ovary / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000009:adverse effects / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014599:Uterus / Q000473:pathology
D001572:Benzofurans; D006846:Hydrocarbons, Halogenated; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1