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

We examined elfects of dietary soy protein isolate (SPI) or genistein (GEN; soy isoflavone) during pregnancy on developinent of colon cancer in inale progeny Sprague-Dawley rats. Four groups ofrats were used: a lifetirne casein-fed group (CAS; control diet), a lifetime SPI-fed group (positive control for protective effect ofdiet on colon carcinogenesis), a group whose dams received SPI only during pregnancy and CAS thereafter (SPUCAS), 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 azoxyrnethane (AOM). Turnors, endocrine status, and colon gene expression were evaluated at 20 week post-AOM. The SPI group had 47% decreased colon turnor 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 minor multiplicity and colon tissue gene expression, and serum IGF-I and testosterone in progeny rats as later adults.