Fetal programming of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone.
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.
Xiao
Rijin
R
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Hennings
Leah J
LJ
Badger
Thomas M
TM
Simmen
Frank A
FA
D000818:Animals; D000831:Animals, Newborn; D001397:Azoxymethane; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000032:analysis; D002364:Caseins; D003106:Colon; D003110:Colonic Neoplasms / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D004032:Diet; D005260:Female; D015870:Gene Expression; D019833:Genistein / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006128:Growth / Q000502:physiology*; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D030262:Soybean Proteins / Q000009:adverse effects*; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D017252:CD3 Complex; D002364:Caseins; D051272:Glucose Transporter Type 1; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D030262:Soybean Proteins; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D019833:Genistein; D017526:Receptor, IGF Type 1; D005947:Glucose; D001397:Azoxymethane