title: Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats.
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.
authors: Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany. frank.moeller@tu-dresden.de.
authors: Frank Josef
authors: FJ
authors: Möller
authors: Department of Food Chemistry, Institute for Pharmacy and Food Chemistry, Universität Würzburg, 97074, Würzburg, Germany.
authors: Daniela
authors: D
authors: Pemp
authors: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, 76131, Karlsruhe, Germany.
authors: Sebastian T
authors: ST
authors: Soukup
authors: Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany.
authors: Kathleen
authors: K
authors: Wende
authors: Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany.
authors: Xiajie
authors: X
authors: Zhang
authors: Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany.
authors: Oliver
authors: O
authors: Zierau
authors: Institute for Pathology, University Clinic Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.
authors: Michael H
authors: MH
authors: Muders
authors: Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors: Maarten C
authors: MC
authors: Bosland
authors: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, 76131, Karlsruhe, Germany.
authors: Sabine E
authors: SE
authors: Kulling
authors: Department of Food Chemistry, Institute for Pharmacy and Food Chemistry, Universität Würzburg, 97074, Würzburg, Germany.
authors: Leane
authors: L
authors: Lehmann
authors: Department of Molecular Cell Physiology and Endocrinology, Institute for Zoology, Technische Universität Dresden, 01062, Dresden, Germany.
authors: Günter
authors: G
authors: Vollmer
mesh_terms: D000818:Animals; D004032:Diet; D004958:Estradiol / Q000633:toxicity*; D005260:Female; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011912:Rats, Inbred ACI; D013025:Glycine max / Q000737:chemistry*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects*
chemical_list: D007529:Isoflavones; D004958:Estradiol
keywords: 17β-Estradiol; ACI rats; Carcinogenesis; Dietary isoflavones; Mammary gland