Exp Clin Endocrinol Diabetes 2015; 123 - P03_12
DOI: 10.1055/s-0035-1547639

Lifelong isoflavone exposure and its implications in an experimental breast cancer model

FJ Möller 1, K Wende 1, O Zierau 1, MC Bosland 2, MH Muders 3, S Soukup 4, SE Kulling 4, G Vollmer 1
  • 1Technische Universität Dresden; Institute for Zoology; Molecular Cell Physiology and Endocrinology
  • 2University of Illinois at Chicago; College of Medicine; Department of Pathology
  • 3Universitätsklinik Carl Gustav Carus; Institut für Pathology
  • 4Max Rubner Institut; Sicherheit und Qualität Bei Obst und Gemüse

More and more evidence accumulates that developmental exposure to soy-derived isoflavones (sISO) considerably impacts on health outcomes later in life. The developing mammary gland (MG) for example reacts in a particularly sensitive manner to the exposure to sISO during fetal, neonatal and pubertal development. The aim of our study was to investigate the effects of a prenatally started and continuously sustained sISO exposure on the tumorigenesis of the MG in an estrogen-driven cancer model.

Using an animal experiment in a multigenerational setting breeding pairs of August-Copenhagen Irish (ACI) rats received either a phytoestrogen-free diet (placebo) or a diet supplemented with 500ppm of a well characterized commercial soy extract. In the female offspring, tumorigenesis of the MG was induced by implantation of a 17β-estradiol releasing silastic tube. To monitor the process of tumorigenesis the animals were palpated weekly over a period of 35 wks. With dissection at 35 wks we assessed tumor incidence, latency as well as multiplicity. All tumors were characterized histopathologically. Additionally, we evaluated MG morphology and a molecular marker for proliferation in relation to the sISO plasma level.

In comparison to PE-free nourished females, those that had been chronically exposed to the Novasoy®650 diet showed a reduction in tumor incidence, multiplicity, and tumor latency. In parallel, the sISO exposed females had significantly increased tumor wet weights and tumor volumes. MG differentiation was not affected by sISO exposure as indicated by morphology studies in MG whole mounts.

In conclusion, long-term sISO exposure of ACI rats clearly reduced the overall number of tumors. Those tumors arising in the sISO dietary group grew faster leading to an increased tumor weight and volume at the end of the experiment. Therefore, dietary exposure to sISO from early life stages until adulthood seems to be a critical determinant for breast cancer risk and clinical outcome.