Estrogen Metabolites as Bioreactive Modulators of Tumor Initiators and Promoters

  • Leon Bradlow
  • Nitin T. Telang
  • Michael P. Osborn
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

A role for estrogens in the initiation and promotion of breast and endometrial cancer has been clear for more than 100 years since Beatson demonstrated that oophorectomy induced remissions in breast cancer (1). The details of these responses are still not clear and are under further study.

Keywords

Breast Cancer Estrogen Metabolite Estrogen Metabolism Mouse Mammary Epithelial Cell Catechol Estrogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Beatson, G., On the treatment of inoperable cases of breast cancer by oophorectomy Lancet 2: 104–107 1898.Google Scholar
  2. 2.
    Miyairi, S and Fishman, J. Radiometric analysis of oxidative reactions in aromatization by placental microsomes J. Biol. Chem. 260: 320–325 1985.PubMedGoogle Scholar
  3. 3.
    Fishman, J., Bradlow, H.L., Schneider, J., Anderson, K.E., and Kappas, A. (1980). Radiometric analysis of biological oxidation in man: Sex differences in estradiol metabolism. Proc. Natl. Acad. Sci. 77: 4957–4960.Google Scholar
  4. 4.
    Bradlow, H.L., Michnovicz, J.J., Telang, N.T., Osborne, M.P. and Goldin B.R. Diet, oncogenes and tumor viruses as modulators of estrogen metabolism in vivo and in vitro. Cancer Detect Prev S16: 35–42, 1992.Google Scholar
  5. 5.
    Guengerich, FP Mechanism-based inactivation of human liver microsomal cytochrome P450IIA4 by gestodene Chemical Research in Toxicology 3: 363–371 1990CrossRefGoogle Scholar
  6. 6.
    Galbraith R.A. and Michnovicz, J.J. (1989). The effects of cimetidine on the oxidative metabolism of estradiol. New Engl. J. Med. 321 269–274.PubMedCrossRefGoogle Scholar
  7. 7.
    Anderson, K.E., Kappas, A., Conney, A.H., Bradlow, H.L., and Fishman, J. (1984). The influence of dietary protein and carbohydrate on the principal oxidative biotransformations of estradiol in normal subjects. J. Clin. Endo. Metab. 59 103–107.CrossRefGoogle Scholar
  8. 8.
    Gierthy, J.F., Lincoln, D.W. II, Kampcik, S.J., Dickerman, H.W., Bradlow, H.L., Niwa, T., and Swaneck, G.E. (1988). Enhancement of 2-and 16α-estradiol hydroxylation in MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem. Biophys, Res. Commun. 157 515–520.CrossRefGoogle Scholar
  9. 9.
    Bradlow, H.L., Michnovicz, J.J., Telang, N.T. and Osborne, M.P. 1991 Effect of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12: 1571–1574, 1991.PubMedCrossRefGoogle Scholar
  10. 10.
    Sepkovic, D.W., Bradlow, H.L., Michnovicz, J.J., Murtezani, S., Levy, I. and Osborne, MR. Catechol estrogen production in rat microsomes after treatment with indole-3-carbinol, ascorbigen, or β-napthoflavone: A comparison of stable isotope dilution gas chromatography-mass spectrometry and radiometric methods. Steroids 59: 318–323, 1994.PubMedCrossRefGoogle Scholar
  11. 11.
    Lustig, R., Hershcopf, R.J. and Bradlow, H.L. The impacts of body weight and diet on estrogen metabolism and estrogen-dependent disease. In Adipose Tissue and Reproduction ed. Frisch, R. Karger Press, Zurich, pp. 119–132, 1989.Google Scholar
  12. 12.
    Gordon J, Cantrall WP, Albers HJ, Mauer S, and Stolar SM. Steroids and lipid metabolism. The hypocholesteremic effect of estrogen metabolites. Steroids 4: 267–91 (1964).CrossRefGoogle Scholar
  13. 13.
    Schneider, J., Huh, M.M., Bradlow, H.L. and Fishman, J. Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells. J Biol Chem 259: 4840–4845, 1984.PubMedGoogle Scholar
  14. 14.
    Zhu, BT, Ezelb, EL Liehr, JG. Catechol O-methyl transferase catalyzes O-methylation of mutagenic flavonoids: Metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo J. Biol. Chem. 269: 292–299 1994.PubMedGoogle Scholar
  15. 15.
    Li, S.A., Li, J.J., Metabolism of moxestrol in the hamster kidney: significance for estrogen carcinogenesis in Hormonal Carcinogenesis, Li, J.J., Nandi, S., and Li, S.A., eds. Springer-Verlag New york, p 110 1992.Google Scholar
  16. 16.
    Shen, Z, Lie, J., Wells, R.L., and Elkind, M.M. CDNA cloning, sequence analysis, and induction by aryl hydrocarbons of a murine cytochroome P450 gene CyplBl DNA Cell Biol 12: 763–9 1994Google Scholar
  17. 17.
    Bradlow, HL Unpublished observations from this laboratory’.Google Scholar
  18. 18.
    Zhu, B.T., Bui, Q.D., Weisz, J, Liehr, J.C. Conversion of estrone to 2-and 4-hydroxyestrone by hamster liver and kidney microsomes: Implications for the mechanism of estrogen induced carcinogenesis. Endocrinol. 135: 1772–1779 1994.CrossRefGoogle Scholar
  19. 19.
    Jellinck P.H. and Bradlow H.L. Peroxidase-catalysed displacement of tritium from regio-specifically labeled estradiol and 2.-hydroxyestradiol. J Steroid Biochem 35: 705–710, 1990.PubMedCrossRefGoogle Scholar
  20. 20.
    Musey, P.I., Collins, D.C., Bradlow, H.L., Gould, K.G., and Preedy, J.K.R. Effect of diet on oxidation of 17β-estradiol in vivo. J. Clin. Endo. Metab 65 792–796 1987.CrossRefGoogle Scholar
  21. 21.
    Osborne, M.P., Bradlow, H.L., Wong, G.Y. and Telang, N.T. Increase in the extent of estradiol 16α-hydroxylation in human breast tissue: A potential biomarker of breast cancer risk. J Natl Cancer Inst 85: 1917–1920, 1993.PubMedCrossRefGoogle Scholar
  22. 22.
    Auborn K.J., Woodworth, C, DiPaolo, J.A. and Bradlow, H.L. The interaction between HPV infection and estrogen metabolism in cervical carcinogenesis Inst. J. Cancer 49: 867–869, 1991.Google Scholar
  23. 23.
    Bradlow, H.L., Hershcopf, R.J., Martucci, C.P., and Fishman, J. Estradiol 16α-hydroxylation in the mouse correlates with mammary tumor incidence and presence of MMTV: a possible model for hormonal etiology of breast cancer in humans. Proc. Natl. Acad. Sci. USA 82 6295–6299 1985.PubMedCrossRefGoogle Scholar
  24. 24.
    Suto, A., Bradlow, H.L., Wong, G.Y., Osborne, M.P. and Telang, N.T. Persistent estrogen responsiveness of Ras oncogene-transformed mouse mammary epithelial cells. Steroids 57: 262–268, 1992.PubMedCrossRefGoogle Scholar
  25. 25.
    Telang, N.T., Arcuri, F., Granata, O.M., Bradlow, H.L., Osborne, M.P. and Castagnetta, L. Alteration of estradiol metabolism in myc oncogene-transfected mouse mammary epithelial cells. Breast Cancer Res Treat, 1994 in press.Google Scholar
  26. 26.
    Han, X, Liehr, JC 8-Hydroxylation of guanine bases in kidney and liver DNA of hamsters treated with estradiol: Role of free radicals in estrogen induced carcinogenesis Cancer Res. 54: 5515–5517 1994.PubMedGoogle Scholar
  27. 27.
    Suto, A., Bradlow, H.L., Wong, G.Y., Osborne, M.P., and Telang, N.T. Experimental down-regulation of intermediate biomarkers of carcinogenesis in mouse mammary epithelial cells. Breast Cancer Res Treat 27: 193–202 1993.PubMedCrossRefGoogle Scholar
  28. 28.
    Dwivedy, I., Devaneson, P., Cremonesi, P., Rogan. E., and Cavalieri, E. Synthesis and Characterization of Estrogen 2,3-and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus Horseradish peroxidase-activated catechol estrogens. Chem. Res Toxicol 9: 828–833 1992.CrossRefGoogle Scholar
  29. 29.
    Li, JJ, Li, SA, Oberley, TG, and Parsons, JA 1995, Carcinogenic Activities of Various Steroidal and Nonsteroidal Estrogens in the Hamster Kidney: Relation to Hormonal Activity and Cell Proliferation. Cancer Res 55 4347–4351.PubMedGoogle Scholar
  30. 30.
    Bradlow HL, Michnovicz JJ, Telang NT, et al: Diet, oncogenes and tumor viruses as modulators of estrogen metabolism in vivo and in vitro. Cancer Detect Prev S16: 35-42, 1992.Google Scholar
  31. 31.
    Kojima T, Tanaka T, Mori M: Chemoprevention of spontaneous endometrial cancer in female Donryku rats by dietary indole-3-carbinol Cancer Res. 54: 1446–1449, 1994.PubMedGoogle Scholar
  32. 32.
    Malloy, V, Bradlow, HL, Matias, J, Orentreich, N: Further studies on chemoprevention of mammary tumors with indole-3-carbinol Terra Symposium on Estrogens 1991. Abst #24.Google Scholar
  33. 33.
    Grubbs C, Steele VE, Casebolt T, et al: Chemoprevention of chemically induced mammary carcinogenesis by indole-3-carbinol AACR Meeting 1994 Abst #1305.Google Scholar
  34. 34.
    Neufield L, Goldsmith A, Bradlow HL, Auborn K: Estrogen metabolism and human papilloma virus-induced tumors of the larynx: Chemoprophylaxis with indole-3-carbinol. Anticancer Res. 13: 227–234 1993.Google Scholar
  35. 35.
    Schneider, J., Kinne, D., Fracchia, A., Pierce, V., Anderson, K.E., Bradlow, H.L. and Fishman, J. Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc Natl Acad Sci USA, 79: 3047–3051, 1982.PubMedCrossRefGoogle Scholar
  36. 36.
    Osborne M.P., Karmali R.A., Hershcopf R.J., Bradlow H.L., Kourides I.A., Williams W.R., Rosen P.P. and Fishman J. Omega-3 fatty acids: Modulation of estrogen metabolism and potential for breast cancer prevention. Cancer Invest 8: 629–631, 1988.CrossRefGoogle Scholar
  37. 37.
    Bradlow, H.L., Hershcopf, R.J., Martucci, C.P. and Fishman, J. Estradiol 16a-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: A possible model for the hormonal etiology of breast cancer in humans. Proc Natl Acad Sci USA, 82: 6295–6299, 1985.PubMedCrossRefGoogle Scholar
  38. 38.
    Telang, N.T., Narayanan. R., Bradlow. H.L. and Osborne, M.P. Coordinated expression of intermediate biomarkers for tumorigenic transformation in Ras-transfected mouse mammary epithelial cells. Breast Cancer Res Treat 18: 155–163, 1991.PubMedCrossRefGoogle Scholar
  39. 39.
    Telang, N.T., Kurihara, H., Wong, G.T.C., Bradlow, H.L., Osborne, M.P. Preneoplastic transformation in mouse mammary tissue: Identification and validation of intermediate biomarkers for chemoprevention Anticancer Res. 11: 1021–1028 1991.PubMedGoogle Scholar
  40. 40.
    Telang, N.T., Bradlow, H.L. and Osborne, M.P. Molecular and endocrine biomarkers in noninvolved breast: Relevance to cancer chemoprevention. J Cell Biochem S 16 G: 161–169, 1992.CrossRefGoogle Scholar
  41. 41.
    Telang, N.T., Suto, A., Wong, G. Y., Osborne, M.P. and Bradlow, H.L. Estrogen metabolite 16α-hydroxyestrone induces genotoxic damage and aberrant cell proliferation in mouse mammary epithelial cells in culture. J Natl Cancer Inst 84: 634–638, 1992.PubMedCrossRefGoogle Scholar
  42. 42.
    Private communication from Dr. Suto.Google Scholar
  43. 43.
    Anderson, K.E., Kappas, A., Conney, A.H., Bradlow, H.L. and Fishman, J. The influence of dietary protein and carbohydrate on the principal oxidative biotransformations of estradiol in normal subjects. J Clin Endocrinol Metab 59: 103–107, 1984.PubMedCrossRefGoogle Scholar
  44. 44.
    Bradlow, H.L., Michnovicz, J.J., Wong, G.Y.C., Halper, M.P, Miller, D. and Osborne, M.P. Long term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prevention 3 591–595, 1994.Google Scholar
  45. 45.
    Lustig, R.H., Bradlow, H.L. and Fishman, J. Estrogen metabolism in disorders of nutrition and dietary composition. In: The Menstrual Cycle and Its Disorders, eds. H.M. Pirke, J. Wuttke and U. Schweiger, Springer-Verlag, Berlin, Heidelberg. pp 119–132, 1989.CrossRefGoogle Scholar
  46. 46.
    Snow, R., Barbieri, R., and Frisch, R., Estrogen 2-hydroxylase oxidation and menstrual function among elite oarswomen J. Clin.Endocrinol. and Metab., 69: 369–376 1991.CrossRefGoogle Scholar
  47. 47.
    Michnovicz, J.J., Hershcopf, R.J., Naganuma, H., Bradlow, H.L. and Fishman, J. Increased 2-hydroxylation of estradiol as a possible mechanism for the antiestrogenic effect of cigarette smoking. N Engl J Med 315: 1305–1309, 1986.PubMedCrossRefGoogle Scholar
  48. 48.
    Gierthy, J.F., Lincoln, D.W. II, Kampcik, S.J., Dickerman, H.W., Bradlow, H.L., Niwa, T. and Swaneck, G.E. Induction of human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Biophys Res Commun 157: 50–55 1988.CrossRefGoogle Scholar
  49. 49.
    Niwa, T., Swaneck, G. and Bradlow, H.L. Alterations in estradiol metabolism in MCF-7 cells induced by treatment with indole-3-carbinol and related compounds. Steroids 59 523–527 1994.PubMedCrossRefGoogle Scholar
  50. 50.
    Bradlow, H.L., Michnovicz, J.J., Telang, N.T. and Osborne, M.P. Effect of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12: 1571–1574, 1991.PubMedCrossRefGoogle Scholar
  51. 51.
    Michnovicz, JJ and Bradlow, HL. Induction of estradiol metabolism by indole-3-carbinol in humans J. Natl Cancer Instit. 82: 947–951 1990.CrossRefGoogle Scholar
  52. 52.
    Michnovicz, JJ. and Bradlow, H.L. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 16: 59–66, 1991.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Leon Bradlow
    • 1
  • Nitin T. Telang
    • 1
  • Michael P. Osborn
    • 1
  1. 1.Strang Cornell Cancer Research LaboratoryNew YorkUSA

Personalised recommendations