Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2007
Publication Date: 10/1/2007
Citation: Xiao, R., Hennings, L., Badger, T.M., Simmen, F.A. 2007. Fetal programming of colon cancer in adult rats: Correlations with altered neonatal trajectory, circulating IGF-I and IGFPBs, and testosterone. Journal of Endocrinology. 195(1):79-87.
Interpretive Summary: The consumption of soy foods has been correlated with reductions in occurrence of cancers in Asian populations. This study evaluated beneficial effects of lifelong soy protein consumption on colon cancer using an established rat model for this devastating disease. Our results showed that lifelong consumption of a soy protein diet inhibited the occurrence of colon cancer when compared to a control diet in this animal model. In addition, feeding of soy protein to rats only during pregnancy led to long-lasting changes in colon cancer development in their progeny as well as long-lasting effects on colon gene expression. Our results suggest that different dietary proteins consumed during pregnancy can elicit quite disparate effects when compared to lifelong consumption and with long-lasting effects in progeny. Lifelong soy consumption may indeed be preventative for colon cancer development.
Technical Abstract: Lifelong consumption of soy protein isolate (SPI) reduces the incidence of azoxymethane (AOM)-induced colon tumors in adult male Sprague-Dawley rats. We determined if a maternal SPI diet during pregnancy could protect against colon cancer in progeny. Four groups of male rats were used: a lifetime casein-fed group (CAS), a lifetime SPI-fed group (SPI), a group whose dams received SPI only during pregnancy and CAS thereafter (SPI/CAS), and a group whose dams received CAS + genistein (soy isoflavone) only during pregnancy and CAS thereafter (GEN/CAS). At 47 and 55 days of age, animals were administered AOM. Tumors, endocrine status, and colonic gene expression were evaluated at 20 wk post-AOM. The SPI group had 36% decreased colon tumor incidence compared to CAS animals (P < 0.05), whereas SPI/CAS, GEN/CAS, and CAS groups did not differ. Maternal SPI increased the percentage of animals bearing multiple colon tumors (P < 0.05), compared to all other groups. Serum insulin and leptin concentrations were decreased in the SPI group (P < 0.05), whereas serum IGF-I was elevated in the SPI/CAS group (P < 0.05). The SPI/CAS group had reduced serum testosterone levels (P < 0.05) compared to all other groups. This same group tended to have up-regulated colonic IGF-I receptor (Igf1r) and glucose transporter-1 (SLC2A1) mRNAs. Results indicate a dietary effect during pregnancy on programming of colon genes and colon cancer development in progeny as later adults. Programmed changes in circulating IGF-I and testosterone may underlie the increased colon tumor multiplicity in this model.