Carcinogenesis Advance Access published online on December 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl240
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In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis
1 Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202
2 Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202
3 To whom correspondence should be addressed at: Arkansas Children's Nutrition Center, 1120 Marshall Street, Little Rock, AR 72202 Tel: +1 501 364-2849, Fax: +1 501 364-3161; E-mail: simmenrosalia{at}uams.edu
The linkage of nutrition and cancer prevention is an intriguing concept that is gaining widespread support. Here, we investigated the influence of developmental context on dietary protection against tumorigenesis initiated by the direct-acting carcinogen N-methyl-N-nitrosourea (NMU), and examined potential mechanisms underlying these effects. Rats were exposed only in utero or for lifetime to AIN-93G diets made with casein (CAS), soy protein isolate (SPI) or CAS supplemented with GEN (GEN). Mammary glands of postnatal day (PND) 50 rats prior to NMU administration were examined for apoptotic status, pro-apoptotic gene expression, and immunoreactive PTEN and E-cadherin levels, while mammary tumor parameters were evaluated 99 days post-NMU. Animals exposed only in utero to SPI had increased tumor latency, decreased tumor multiplicity, and lower higher grade tumors, than those fed CAS. In utero exposure to GEN resulted in similar tumor parameters as the CAS group, while lifetime SPI exposure decreased tumor incidence that was not mimicked by in utero exposure alone. Mammary glands of PND50 rats fed lifetime SPI had increased TEB apoptotic status and PTEN expression, than the other diet groups. Rats exposed only in utero to SPI or GEN had higher membrane E-cadherin in mammary structures than those lifetime fed CAS or SPI. Thus, limited exposure during gestation to soy protein isolate can positively influence resistance to chemically-induced mammary tumorigenesis later in life. Preventative strategies against mammary and other types of cancer might be uncovered by refinement of the developmental window for dietary factor exposure.
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