Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1997 Jul;105(7):750–755. doi: 10.1289/ehp.97105750

Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls.

K L Johnson 1, A M Cummings 1, L S Birnbaum 1
PMCID: PMC1470109  PMID: 9294722

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 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.

Full text

PDF
750

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bandiera S., Sawyer T. W., Campbell M. A., Fujita T., Safe S. Competitive binding to the cytosolic 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor. Effects of structure on the affinities of substituted halogenated biphenyls--a QSAR analysis. Biochem Pharmacol. 1983 Dec 15;32(24):3803–3813. doi: 10.1016/0006-2952(83)90153-3. [DOI] [PubMed] [Google Scholar]
  2. Barsotti D. A., Abrahamson L. J., Allen J. R. Hormonal alterations in female rhesus monkeys fed a diet containing 2, 3,7,8-tetrachlorodibenzo-p-dioxin. Bull Environ Contam Toxicol. 1979 Mar;21(4-5):463–469. doi: 10.1007/BF01685454. [DOI] [PubMed] [Google Scholar]
  3. Birnbaum L. S., DeVito M. J. Use of toxic equivalency factors for risk assessment for dioxins and related compounds. Toxicology. 1995 Dec 28;105(2-3):391–401. doi: 10.1016/0300-483x(95)03237-a. [DOI] [PubMed] [Google Scholar]
  4. Birnbaum L. S. The mechanism of dioxin toxicity: relationship to risk assessment. Environ Health Perspect. 1994 Nov;102 (Suppl 9):157–167. doi: 10.1289/ehp.94102s9157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Brewster D. W., Birnbaum L. S. Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat. Toxicol Appl Pharmacol. 1987 Sep 15;90(2):243–252. doi: 10.1016/0041-008x(87)90332-2. [DOI] [PubMed] [Google Scholar]
  7. Cummings A. M., Metcalf J. L., Birnbaum L. Promotion of endometriosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats and mice: time-dose dependence and species comparison. Toxicol Appl Pharmacol. 1996 May;138(1):131–139. doi: 10.1006/taap.1996.0106. [DOI] [PubMed] [Google Scholar]
  8. Cummings A. M., Metcalf J. L. Effects of estrogen, progesterone, and methoxychlor on surgically induced endometriosis in rats. Fundam Appl Toxicol. 1995 Sep;27(2):287–290. doi: 10.1006/faat.1995.1135. [DOI] [PubMed] [Google Scholar]
  9. Cummings A. M., Metcalf J. L. Induction of endometriosis in mice: a new model sensitive to estrogen. Reprod Toxicol. 1995 May-Jun;9(3):233–238. doi: 10.1016/0890-6238(95)00004-t. [DOI] [PubMed] [Google Scholar]
  10. DeVito M. J., Birnbaum L. S. The importance of pharmacokinetics in determining the relative potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran. Fundam Appl Toxicol. 1995 Jan;24(1):145–148. doi: 10.1006/faat.1995.1016. [DOI] [PubMed] [Google Scholar]
  11. Goldstein J. A., Weaver R., Sundheimer D. W. Metabolism of 2-acetylaminofluorene by two 3-methylcholanthrene-inducible forms of rat liver cytochrome P-450. Cancer Res. 1984 Sep;44(9):3768–3771. [PubMed] [Google Scholar]
  12. Hanson C. D., Smialowicz R. J. Evaluation of the effect of low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on cell mediated immunity. Toxicology. 1994 Mar 11;88(1-3):213–224. doi: 10.1016/0300-483x(94)90122-8. [DOI] [PubMed] [Google Scholar]
  13. Kafafi S. A., Afeefy H. Y., Said H. K., Hakimi J. M. A new structure-activity model for Ah receptor binding. Polychlorinated dibenzo-p-dioxins and dibenzofurans. Chem Res Toxicol. 1992 Nov-Dec;5(6):856–862. doi: 10.1021/tx00030a020. [DOI] [PubMed] [Google Scholar]
  14. Kociba R. J., Keeler P. A., Park C. N., Gehring P. J. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): results of a 13-week oral toxicity study in rats. Toxicol Appl Pharmacol. 1976 Mar;35(3):553–574. doi: 10.1016/0041-008x(76)90078-8. [DOI] [PubMed] [Google Scholar]
  15. Koninckx P. R., Braet P., Kennedy S. H., Barlow D. H. Dioxin pollution and endometriosis in Belgium. Hum Reprod. 1994 Jun;9(6):1001–1002. doi: 10.1093/oxfordjournals.humrep.a138623. [DOI] [PubMed] [Google Scholar]
  16. Koninckx P. R., Meuleman C., Demeyere S., Lesaffre E., Cornillie F. J. Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain. Fertil Steril. 1991 Apr;55(4):759–765. doi: 10.1016/s0015-0282(16)54244-7. [DOI] [PubMed] [Google Scholar]
  17. Li X., Johnson D. C., Rozman K. K. Reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female rats: ovulation, hormonal regulation, and possible mechanism(s). Toxicol Appl Pharmacol. 1995 Aug;133(2):321–327. doi: 10.1006/taap.1995.1157. [DOI] [PubMed] [Google Scholar]
  18. Lundberg K., Dencker L., Grönvik K. O. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits the activation of antigen-specific T-cells in mice. Int J Immunopharmacol. 1992 May;14(4):699–705. doi: 10.1016/0192-0561(92)90133-6. [DOI] [PubMed] [Google Scholar]
  19. Mason G., Farrell K., Keys B., Piskorska-Pliszczynska J., Safe L., Safe S. Polychlorinated dibenzo-p-dioxins: quantitative in vitro and in vivo structure-activity relationships. Toxicology. 1986 Oct;41(1):21–31. doi: 10.1016/0300-483x(86)90101-0. [DOI] [PubMed] [Google Scholar]
  20. Mayani A., Barel S., Soback S., Almagor M. Dioxin concentrations in women with endometriosis. Hum Reprod. 1997 Feb;12(2):373–375. doi: 10.1093/humrep/12.2.373. [DOI] [PubMed] [Google Scholar]
  21. Morrow P. E. Dust overloading of the lungs: update and appraisal. Toxicol Appl Pharmacol. 1992 Mar;113(1):1–12. doi: 10.1016/0041-008x(92)90002-a. [DOI] [PubMed] [Google Scholar]
  22. Okey A. B., Riddick D. S., Harper P. A. Molecular biology of the aromatic hydrocarbon (dioxin) receptor. Trends Pharmacol Sci. 1994 Jul;15(7):226–232. doi: 10.1016/0165-6147(94)90316-6. [DOI] [PubMed] [Google Scholar]
  23. Olive D. L., Schwartz L. B. Endometriosis. N Engl J Med. 1993 Jun 17;328(24):1759–1769. doi: 10.1056/NEJM199306173282407. [DOI] [PubMed] [Google Scholar]
  24. Pohjanvirta R., Tuomisto J. Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals: effects, mechanisms, and animal models. Pharmacol Rev. 1994 Dec;46(4):483–549. [PubMed] [Google Scholar]
  25. Poland A., Glover E. Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent inducer of aryl hydrocarbon hydroxylase, with 3-methylcholanthrene. Mol Pharmacol. 1974 Mar;10(2):349–359. [PubMed] [Google Scholar]
  26. Rier S. E., Martin D. C., Bowman R. E., Dmowski W. P., Becker J. L. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundam Appl Toxicol. 1993 Nov;21(4):433–441. doi: 10.1006/faat.1993.1119. [DOI] [PubMed] [Google Scholar]
  27. Safe S. H. Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans. Annu Rev Pharmacol Toxicol. 1986;26:371–399. doi: 10.1146/annurev.pa.26.040186.002103. [DOI] [PubMed] [Google Scholar]
  28. Safe S. Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol. 1990;21(1):51–88. doi: 10.3109/10408449009089873. [DOI] [PubMed] [Google Scholar]
  29. Umbreit T. H., Hesse E. J., Macdonald G. J., Gallo M. A. Effects of TCDD-estradiol interactions in three strains of mice. Toxicol Lett. 1988 Jan;40(1):1–9. doi: 10.1016/0378-4274(88)90177-4. [DOI] [PubMed] [Google Scholar]
  30. Vernon M. W., Wilson E. A. Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985 Nov;44(5):684–694. [PubMed] [Google Scholar]
  31. Whitlock J. P., Jr Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. Annu Rev Pharmacol Toxicol. 1990;30:251–277. doi: 10.1146/annurev.pa.30.040190.001343. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES