Influence of Prevastein, an isoflavone-rich soy product, on mammary gland development and tumorigenesis in Tg.NK (MMTV/c-neu) mice.
We investigated spontaneous mammary tumor development and mammary gland morphogenesis in female Tg.NK mice postnatally exposed to dietary soy isoflavones (0, 11, 39, and 130 mg aglycones/kg diet) added to a Western-style diet. Instead of preventing mammary tumorigenesis, the highest dose of isoflavones was associated with a small but significant increase in the number and size of tumors as compared to mice administered a Western-style control diet (P < 0.05). At postnatal Week 6, dynamic activity (measured as apoptotic density) at the highest dose and the degree of branching of the mammary tree in all isoflavone-exposed groups was increased as compared to controls (P < 0.05). At adulthood, the epithelium appeared more quiescent in the medium- and high-dose groups evident by reduced apoptotic density and a reduction in the percentage of terminal end buds (TEBs), respectively, as compared to controls (P < 0.05). The number of actively dividing cells within the TEBs was unaffected by isoflavone exposure as was the activity of drug-metabolizing and antioxidant enzymes. In conclusion, isoflavones may augment mammary gland and mammary tumor development.
Thomsen
Anni R
AR
Danish Institute for Food and Veterinary Research, Department of Toxicology and Risk Assessment, Søborg, Denmark.
Mortensen
Alicja
A
Breinholt
Vibeke M
VM
Lindecrona
Rikke H
RH
Peñalvo
José L
JL
Sørensen
Ilona K
IK
D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior; D005260:Female; D007150:Immunohistochemistry; D007529:Isoflavones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development*; D008325:Mammary Neoplasms, Experimental / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011897:Random Allocation; D013025:Glycine max / Q000737:chemistry*
D007529:Isoflavones; D018809:Proliferating Cell Nuclear Antigen