Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens.
Breast cancer is a major public health problem among women worldwide. Phytoestrogens and dietary fat composition are being investigated to elucidate the role of nutrition in breast cancer risk. Both epidemiological and rodent studies suggest that the chemopreventive effect of phytoestrogens depends on timing of exposure. We investigated spontaneous mammary tumor development in female heterozygous MMTV/c-neu (Tg.NK) mice upon isoflavone exposure on background diets rich in either n-6 or n-3 polyunsaturated fatty acids (PUFAs). Three different exposure protocols were used, either from conception to weaning, or from weaning onwards, or lifelong. Mice fed diets high in n-3 PUFAs developed mammary tumors 15 weeks later than mice fed n-6 PUFA diets. In the latter mice, isoflavone exposure from weaning onwards resulted in a significant decrease in tumor incidence and a delay in tumor onset. Therefore, the effects of phytoestrogen exposure on tumor formation appear to depend on the composition of the background diet and on the timing of exposure within the life cycle.
Luijten
Mirjam
M
Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. Mirjam.Luijten@rivm.nl
Verhoef
Aart
A
Dormans
Jan A M A
JA
Beems
Rudolf B
RB
Cremers
Hans W J M
HW
Nagelkerke
Nico J D
NJ
Adlercreutz
Herman
H
Peñalvo
José L
JL
Piersma
Aldert H
AH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000633:toxicity; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000737:chemistry / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D049590:Postpartum Period; D011247:Pregnancy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013997:Time Factors; D014886:Weaning
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D007529:Isoflavones; D048789:Phytoestrogens; D018719:Erb-b2 Receptor Tyrosine Kinases