title: Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary tumor development in Tg.NK (MMTV/c-neu) mice.
abstract: Phytoestrogens such as isoflavonoids and lignans have been postulated as breast cancer protective constituents in soy and whole-grain cereals. We investigated the ability of isoflavones (IFs) and flaxseed to modulate spontaneous mammary tumor development in female heterozygous Tg.NK (MMTV/c-neu) mice. Two different exposure protocols were applied, either from 4 wk of age onward (postweaning) or during gestation and lactation (perinatal). In the postweaning exposure study, mice were fed IFs or flaxseed in a high-fat diet. In addition, flaxseed in a low-fat diet was tested. Postweaning exposure to IFs and flaxseed tended to accelerate the onset of mammary adenocarcinoma development, although tumor burden at necropsy was not changed significantly. Perinatal IF exposure resulted in enhanced mammary gland differentiation, but palpable mammary tumor onset was not affected. However, tumor burden at necropsy in the perinatal exposure study was significantly increased in the medium- and high-IF dose groups. Comparison of both exposure scenarios revealed a strongly accelerated onset of tumor growth after perinatal high-fat diet exposure compared with the low-fat diet. This study shows that breast cancer-modulating effects of phytoestrogens are dependent both on the background diet and on the timing of exposure in the life cycle.
authors.affiliation: Laboratory of Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. mirjam.luijten@rivm.nl
authors.forename: Mirjam
authors.initials: M
authors.lastname: Luijten
authors.forename: Anni Rønfeldt
authors.initials: AR
authors.lastname: Thomsen
authors.forename: Jolanda A H
authors.initials: JA
authors.lastname: van den Berg
authors.forename: Piet W
authors.initials: PW
authors.lastname: Wester
authors.forename: Aart
authors.initials: A
authors.lastname: Verhoef
authors.forename: Nico J D
authors.initials: NJ
authors.lastname: Nagelkerke
authors.forename: Herman
authors.initials: H
authors.lastname: Adlercreutz
authors.forename: Henk J
authors.initials: HJ
authors.lastname: van Kranen
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.forename: Ilona K
authors.initials: IK
authors.lastname: Sørensen
authors.forename: Ghanta N
authors.initials: GN
authors.lastname: Rao
authors.forename: Coen F
authors.initials: CF
authors.lastname: van Kreijl
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D019597:Flax; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage*; D007774:Lactation; D008325:Mammary Neoplasms, Experimental / Q000453:epidemiology*; D051379:Mice; D008822:Mice, Transgenic; D048789:Phytoestrogens / Q000008:administration & dosage* / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D013025:Glycine max / Q000737:chemistry*; D014886:Weaning
chemical_list: D004041:Dietary Fats; D007529:Isoflavones; D048789:Phytoestrogens