Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary tumor development in Tg.NK (MMTV/c-neu) mice.
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.
Luijten
Mirjam
M
Laboratory of Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. mirjam.luijten@rivm.nl
Thomsen
Anni Rønfeldt
AR
van den Berg
Jolanda A H
JA
Wester
Piet W
PW
Verhoef
Aart
A
Nagelkerke
Nico J D
NJ
Adlercreutz
Herman
H
van Kranen
Henk J
HJ
Piersma
Aldert H
AH
Sørensen
Ilona K
IK
Rao
Ghanta N
GN
van Kreijl
Coen F
CF
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
D004041:Dietary Fats; D007529:Isoflavones; D048789:Phytoestrogens