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Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats

  • Toxicokinetics and Metabolism
  • Published:
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Abstract

There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened.

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Acknowledgments

The authors are grateful to Dr. Carolin Kleider for help in determining E2 levels in the implants and for performing the UHPLC-MS/MS analysis of estrogens in plasma, to Antje Beyer for support with the animal experiments and technical assistance, and to Dr. Katja Schmalbach for assistance with the biostatistical analysis. This work is part of the joint research project, IsoCross, entitled, ‘Isoflavones: Cross-species comparison of metabolism, estrogen sensitivity, epigenetics and carcinogenesis’ that is funded by the German Research Foundation (Grants: VO 410/12-1, KU 1079/10–1, LE 1329/10–1).

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Authors and Affiliations

  1. Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany

    Frank Josef Möller, Kathleen Wende, Xiajie Zhang, Oliver Zierau & Günter Vollmer

  2. Department of Food Chemistry, Institute for Pharmacy and Food Chemistry, Universität Würzburg, 97074, Würzburg, Germany

    Daniela Pemp & Leane Lehmann

  3. Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, 76131, Karlsruhe, Germany

    Sebastian T. Soukup & Sabine E. Kulling

  4. Institute for Pathology, University Clinic Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany

    Michael H. Muders

  5. Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA

    Maarten C. Bosland

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  1. Frank Josef Möller
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  2. Daniela Pemp
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Correspondence to Frank Josef Möller.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Möller, F.J., Pemp, D., Soukup, S.T. et al. Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats. Arch Toxicol 90, 1907–1916 (2016). https://doi.org/10.1007/s00204-016-1674-2

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