Biological Trace Element Research

, Volume 121, Issue 2, pp 160–170 | Cite as

Experimental Study on the Estrogen-Like Effect of Boric Acid

Article

Abstract

There are now considerable evidences that boric acid has reproductive and developmental toxicity, but it is uncertain whether such toxicity is caused by estrogen-like effect. Our objective is to determine the estrogen-like effect of boric acid. Proliferation assay of MCF-7 human breast cancer cells, uterotrophic assay, measure assay of the estradiol (E2), proliferation assay of mucous membrane cells, and assay of estrogen receptor were conducted in this study. Boric acid could increase the weight of uterus of ovariectomized SD rats and the height of epithelium cells of mucous membrane, enhance the expression of the proliferating cell nucleus antigen, and reduce the density of estrogen receptors. However, boric acid could not affect the level of estradiol in serum and stimulate the proliferation of MCF-7 human breast cancer cells. In this study, boric acid exhibited the estrogen-like effect in vivo.

Keywords

Boric acid Proliferation assay of MCF-7 human breast cancer cells Uterotrophic assay Proliferation assay in mucous membrane Estrogen receptor (ER) 

References

  1. 1.
    Brevini TA, Cillo F, Antonini S, Gandolfi F (2005) Effects of endocrine disrupters on the oocytes and embryos of farm animals. Reprod Domest Anim 40:291–299PubMedCrossRefGoogle Scholar
  2. 2.
    Cravedi JP, Zalko D, Savouret JF, Menuet A, Jégou B (2007) The concept of endocrine disruption and human health. Med Sci (Paris) 23:198–204Google Scholar
  3. 3.
    Watson CS, Campbell CH, Gametchu B (1999) Membrane oestrogen receptors on rat pituitary tumour cells: immunoidentification and responses to oestradiol and xenoestrogens. Exp Physiol 84:1013–1022PubMedCrossRefGoogle Scholar
  4. 4.
    Aravindakshan J, Paquet V, Gregory M, Dufresne J, Fournier M, Marcogliese DJ, Cyr DG (2004) Consequences of xenoestrogen exposure on male reproductive function in spottail shiners (Notropis hudsonius). Toxicol Sci 78:156–165PubMedCrossRefGoogle Scholar
  5. 5.
    Wozniak AL, Bulayeva NN, Watson CS (2005) Xeno-estrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells. Environ Health Perspect 113:431–439PubMedCrossRefGoogle Scholar
  6. 6.
    Humfrey CD (1998) Phytoestrogens and human health effects: weighing up the current evidence. Nat Toxins 6:51–59PubMedCrossRefGoogle Scholar
  7. 7.
    Wide M, Wide L (1980) Estradiol receptor activity in uteri of pregnant mice given lead before implantation. Fertil Steril 34:503–508PubMedGoogle Scholar
  8. 8.
    Garcia-Morales P, Saceda M, Kenney N, Kim N, Salomon DS, Gottardis MM, Solomon HB, Sholler PF, Jordan VC, Martin MB (1994) Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells. J Biol Chem 269:16896–16901PubMedGoogle Scholar
  9. 9.
    Folmar LC, Hemmer MJ, Denslow ND, Kroll K, Chen J, Cheek A, Richman H, Meredith H, Grau EG (2002) A comparison of the estrogenic potencies of estradiol, ethynylestradiol, diethylstilbestrol, nonylphenol and methoxychlor in vivo and in vitro. Aquat Toxicol 60:101–110PubMedCrossRefGoogle Scholar
  10. 10.
    Go V, Garey J, Wolff MS, Pogo BG (1999) Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environ Health Perspect 107:173–177PubMedCrossRefGoogle Scholar
  11. 11.
    Okubo T, Suzuki T, Yokoyama Y, Kano K, Kano I (2003) Estimation of estrogenic and anti-estrogenic activities of some phthalate diesters and monoesters by MCF-7 cell proliferation assay in vitro. Biol Pharm Bull 26:1219–1224PubMedCrossRefGoogle Scholar
  12. 12.
    Eui-Ju H, Youn-Kyu J, Kyung-Chul C, Noboru M, Eui-Bae J (2005) Conflict of estrogenic activity by various phthalates between in vitro and in vivo models related to the expression of Calbindin-D9k. J Reprod Dev 51:253–263CrossRefGoogle Scholar
  13. 13.
    Olsen CM, Meussen-Elholm ET, Samuelsen M, Holme JA, Hongslo JK (2003) Effects of the environmental oestrogens bisphenol A, tetrachlorobisphenol A, tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4'-dihydroxybiphenyl on oestrogen receptor binding, cell proliferation and regulation of oestrogen sensitive proteins in the human breast cancer cell line MCF-7. Pharmacol Toxicol 92:180–188PubMedCrossRefGoogle Scholar
  14. 14.
    Rajapakse N, Silva E, Scholze M, Kortenkamp A (2004) Deviation from additivity with estrogenic mixtures containing 4-nonylphenol and 4-tert-octylphenol detected in the E-SCREEN assay. Environ Sci Technol 38:6343–6352PubMedCrossRefGoogle Scholar
  15. 15.
    Bevan CL, Porter DM, Prasad A, Howard MJ, Henderson LP (2003) Environmental estrogens alter early development in Xenopus laevis. Environ Health Perspect 111:448–496Google Scholar
  16. 16.
    Althuis MD, Brogan DR, Coates BJ (2003) Hormonal content and potency of oral contraceptives and breast cancer risk among young women. Br J Cancer 88:50–57PubMedCrossRefGoogle Scholar
  17. 17.
    Sthoeger ZM, Zinger H, Mozes E (2003) Beneficial effects of the anti-oestrogen tamoxifen on systemic lupus erythematosus of (NZBXNZW) F1 female mice are associated with specific reduction of IgGs autoantibodies. AnnRheum Dis 62:341–346CrossRefGoogle Scholar
  18. 18.
    Halldin K (2005) Impact of endocrine disrupting chemicals on reproduction in Japanese quail. Domest Anim Endocrinol 29:420–429PubMedCrossRefGoogle Scholar
  19. 19.
    Ho SM, Tang WY, Belmonte de Frausto J, Prins GS (2006) Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res 66:5624–5632PubMedCrossRefGoogle Scholar
  20. 20.
    Dieter MP (1994) Toxicity and carcinogenicity studies of boric acid in male and female B6C3F 1 mice. Environ Health Perspect 102(Suppl7):93–97PubMedCrossRefGoogle Scholar
  21. 21.
    Loewengart G (2001) Toxicity of boron to rainbow trout: a weight-of-the-evidence assessment. Environ Toxicol Chem 20:796–803PubMedCrossRefGoogle Scholar
  22. 22.
    Barranco WT, Hudak PF, Eckhert CD (2007) Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States). Cancer Causes Control 18:71–77PubMedCrossRefGoogle Scholar
  23. 23.
    Weir RJ, Fisher RS (1972) Toxicologic studies on borax and boric acid. Toxicol Appl Pharmacol 23:351–364PubMedCrossRefGoogle Scholar
  24. 24.
    Kimberley A Treinen Robert E (1991) Development of testicular lesions in F334 rats after treatment with boric acid. Toxicol Appl Pharm 107:325–335CrossRefGoogle Scholar
  25. 25.
    Nielsen FH, Mullen LM, Gallagher SK (1990) Effect of boron depletion and repletion on blood indicators of calcium status in humans fed a magnesium-low diet. J Trace Elem Exp Med 3:45–54Google Scholar
  26. 26.
    Price CJ, Marr MC, Myers CB, Seely JC, Heindel JJ, Schwetz BA (1996) The developmental toxicity of boric acid in rabbits. Fundam Appl Toxicol 34:176–187PubMedCrossRefGoogle Scholar
  27. 27.
    Ku WW, Chapin RE (1994) Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies. Environ Health Perspec 102(Suppl7):99–105CrossRefGoogle Scholar
  28. 28.
    Kudo S, Tanase H, Yamasaki M, Nakao M, Miyata Y, Tsuru K, Imai S (2000) Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 23). A comparative 2- and 4-week repeated oral dose testicular toxicity study of boric acid in rats. J Toxicol Sci 25:223–232PubMedGoogle Scholar
  29. 29.
    Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:110CrossRefGoogle Scholar
  30. 30.
    Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO (1995) The E-screen assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ Health Perspect 103(suppl 7):113–122PubMedCrossRefGoogle Scholar
  31. 31.
    Martin LA, Farmer I, Johnston SR, Ali S, Marshall C, Dowsett M (2003) Enhanced estrogen receptor (ER) . a. , ERBB2, and MAPK signal transduction pathways operate during the adaptation of MCF-7 cells to long term estrogen deprivation. J Biol Chem 278:30458–30468PubMedCrossRefGoogle Scholar
  32. 32.
    Yu ZL, Zhang LS, Xu PY, Wu DS (2003) The effects of three plastic additives on the proliferation of MCF-7 cell. Chinese Journal Preventive Medicine 37:150–153Google Scholar
  33. 33.
    Jiang JY, Xu Q (2003) Immunomodulatory activity of the aqueous extract from rhizome of Smilax glabra in the later phase of adjuvant-induced arthritis in rats. J Ethnopharmacol 85:53–59PubMedCrossRefGoogle Scholar
  34. 34.
    Ju YH, Clausen LM, Allred KF, Almada AL, Helferich WG (2004) Beta-sitosterol, beta-sitosterol glucoside, and a mixture of beta-sitosterol and beta-sitosterol glucoside modulate the growth of estrogen-responsive breast cancer cells In vitro and in ovariectomized athymic mice. J Nutr 134:1145–1151PubMedGoogle Scholar
  35. 35.
    Diel P, Schulz T, Smolnikar K, Strunck E, Vollmer G, Michna H (2000) Ability of xeno- and phytoestrogens to modulate express of estrogen-sensitive genes in rat uterus: estrogenicity profiles and uterotropic activity. J Steroid Biochem Mol Biol 73:1–10PubMedCrossRefGoogle Scholar
  36. 36.
    Shen LJ, Zhou YF, Jin TY (2001) Experimental study on the estrogen-like effect of cadmium. J Labour Medicine 18:67–69Google Scholar
  37. 37.
    Wang N, Rong SX, ZHou YL, Zhong XJ, Jin TY (2005) Uterotrophic assay of acrylonitrile in rats. J Labour Medicine 22:33–38Google Scholar
  38. 38.
    Kesler DJ, Garverick HA, Youngquist RS, Elmore RG, Bierschwal CJ (1977) Effect of days postpartum and endogenous reproductive hormones on GnRH-induced LH release in dairy cows. J Anim Sci 45:797–803PubMedGoogle Scholar
  39. 39.
    Long GG, Diekman MA (1984) Effect of purified zearalenone on early gestation in gilts. J Anim Sci 59:1662–1670PubMedGoogle Scholar
  40. 40.
    Sun AJ, Zhu PD, Wang JD, Cheng J, Zhang SC, Liu W, Xu RH, Lin SQ, Ge QS (1997) Study the effect of estrogen and progestogen replacement therapy on the proliferation and inhibition of the endometrium: I. Observation of various doses of estradiol valerate on the proliferation of rat endometrium by means of mitosis and proliferating cell nuclear antigen. J Reprod Med 6:32–36Google Scholar
  41. 41.
    Lai MD, Lee LR, Cheng KS, Wing LY (2000) Expression of proliferating cell nuclear antigen in luminal epithelium during the growth and regression of rat uterus. J Endocrinol 166:87–93PubMedCrossRefGoogle Scholar
  42. 42.
    Zhou Q, He Q, Liang LJ (2003) Expression of p27, cyclin E and cyclin A in hepatocellular carcinoma and its clinical significance. World J Gastroenterol 9:2450–2454PubMedGoogle Scholar
  43. 43.
    Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54:138–153PubMedCrossRefGoogle Scholar
  44. 44.
    Bradford MM (1976) A rapid and sensitive method for the quantitation microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  45. 45.
    Zhu GZ, Sun M, Zhang Y, Zhang YL (1996) A comparison between HAP and DCC methods for estrogen receptor measurements. Curr Adv Obstet Gynecol 4:321–323Google Scholar
  46. 46.
    Lv BZ, Lu J, An MB (2000) The science of receptor. The Science and Technology Publishing House of Anhui, ChinaGoogle Scholar
  47. 47.
    Qui J, Chang Y, Zhu X (1999) Use in vivo multiple endpoints assay for studying estrogenicity of endosulfan. Carcinogenesis Teratogenesis and Mutagenesis 11:252–256Google Scholar
  48. 48.
    Soto AM, Chung KL, Sounenschein C (1994) The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect 102:380–383PubMedCrossRefGoogle Scholar
  49. 49.
    Dong JW, Li J, Fan XY, Yao SQ, Wang Y (2005) Screening for estrogenic activities for three pyrethroids with uterotrophic assays. J Environ Occup Med 22:361–383Google Scholar
  50. 50.
    Chen HY, Wang XR, Xiao JG, Hu G, Song L, Wang SL, He FS (2001) Research on estrogenicity of organophosphorus and pyrethroid pesticides. Chin J Ind Hyg Occup Dis 19:274–277Google Scholar
  51. 51.
    Woods WG (1994) An introduction to boron: history, source, users and chemistry. Environ Health Perspect 102(suppl 7):5–11PubMedCrossRefGoogle Scholar
  52. 52.
    ATSDR (1992) Toxicological profile for boron. Agency for Toxic Substances and Disease Registry, Atlanta, GAGoogle Scholar
  53. 53.
    Culver BD, Shen PT, Taylor TH, Lee-Feldstein A, Anton-Culver H, Strong PL (1994) The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker. Environ Health Perspect 102(Suppl 7):133–137PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Department of Toxicology, Zhengzhou University of HenanZhengzhouPeople’s Republic of China
  2. 2.Henan Center for Disease Control and PreventionZhengzhouPeople’s Republic of China

Personalised recommendations