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Journal of Endocrinology (2007) 195, 79-87    DOI: 10.1677/JOE-07-0256
© 2007 Society for Endocrinology

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Fetal programing of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone

Rijin Xiao1,3, Leah J Hennings2, Thomas M Badger1,3 and Frank A Simmen1,3

1 Departments of Physiology and Biophysics and
2 Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
3 The Arkansas Children’s Nutrition Center, University of Arkansas for Medical Sciences, 1212 Marshall Street, Little Rock, Arkansas 72205, USA

(Correspondence should be addressed to F A Simmen; Email: simmenfranka{at}uams.edu)

We examined effects of dietary soy protein isolate (SPI) or genistein (GEN; soy isoflavone) during pregnancy on development of colon cancer in male progeny Sprague–Dawley rats. Four groups of rats were used: a lifetime casein-fed group (CAS; control diet), a lifetime SPI-fed group (positive control for protective effect of diet on colon carcinogenesis), a group whose dams received SPI only during pregnancy and CAS thereafter (SPI/CAS), and a group whose dams received CAS+GEN only during pregnancy and CAS thereafter (GEN/CAS). At 47 and 55 days of age, male progeny were administered the intestinal carcinogen azoxymethane (AOM). Tumors, endocrine status, and colon gene expression were evaluated at 20 week post-AOM. The SPI group had 47% decreased colon tumor incidence compared with the CAS group (P<0.05), whereas SPI/CAS, GEN/CAS, and CAS groups did not differ in this regard. Maternal-only SPI increased the percentage of animals bearing multiple colon tumors (P<0.05), an effect not mimicked by GEN. Serum insulin and leptin concentrations were decreased by lifetime SPI (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) and exhibited a tendency for increased mucosal expression of IGF-I receptor and glucose transporter-1 mRNAs. Results indicate an effect of dietary protein type during pregnancy on colon tumor multiplicity and colon tissue gene expression, and serum IGF-I and testosterone in progeny rats as later adults.







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