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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #187147
Title: DIETS CONTAINING SOY PROTEIN ISOLATE OR THE SOY ISOFLAVONE GENISTEIN SUPPRESS P53-MEDIATED ACTIVATION OF THE COLON DNA DAMAGE RESPONSE PATHWAY IN AZOXYMETHANE (AOM)-TREATED RATS

Author
item GENG, YAN - ACNC/UAMS
item TILL, RENEE - ACNC
item FRANK, JULIE - ACNC
item FERGUSON, MATTHEW - ACNC
item BADGER, THOMAS - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2006
Publication Date: 3/27/2006
Citation: Geng, Y., Till, R.S., Frank, J.A., Ferguson, M., Badger, T.M., Simmen, R.C., Simmen, F.A. 2006. Diets containing soy protein isolate or the soy isoflavone genistein suppress P53-mediated activation of the colon DNA damage response pathway in azoxymethane (AOM)-treated rats [abstract]. The FASEB Journal. 20(4):A564.

Interpretive Summary: This study examined if diets containing soy protein or a constituent of soy, a chemical called genistein, can effect changes in the colon to help repair damage to DNA after treatment with carcinogenic agents. This is an important question to ask, since dietary soy may be beneficial to humans with respect to preventing colon cancer and un-repaired DNA damage is known to cause various types of cancers. Our study indeed demonstrated that soy protein or genistein when fed to rats elicited physiological changes in the colon that are likely to be preventive against cancer-development in this tissue. Future studies will seek to unravel how dietary soy is working in this regard, with the long-term goal being to develop novel nutritional strategies for cancer-prevention.

Technical Abstract: We examined effects of soy protein isolate (SPI) and genistein (GEN) on acute activation of the DNA damage response pathway (detected as increased phospho-p53-ser15) and apoptosis (TUNEL) in male Sprague-Dawley rat colon, after administration of the colon carcinogen AOM. Rats were fed AIN93G diets containing as sole protein source casein (CAS), SPI or CAS + GEN (0.25g/kg). Colons were obtained just prior to and at 1 and 4 days post-AOM. Mid-points of proximal and distal colon were analyzed. Prior to AOM, there were only few phospho-p53-ser15 positive crypt cells in proximal colon (~0.3 cells/crypt) and none in distal colon of all diet groups. At day 1 post-AOM, increased numbers of phospho-p53-ser15 positive cells were observed in crypts of proximal and distal colon, relative to no-AOM control rats (P<0.05). In all groups at 4 days post-AOM, the numbers of phospho-p53-ser15 positive crypt cells were lower than for day 1, but higher than for no-AOM. SPI and GEN rats had fewer phospho-p53-ser15 positive cells in proximal and distal colon at day 1 relative to CAS (30-40% lower, P<0.05). TUNEL results generally followed the same temporal pattern. At day 1 post-AOM, circulating insulin concentrations were reduced by SPI and GEN. Results suggest that SPI and GEN promote a physiological state in the colon that is more resistant to AOM-induced DNA damage and that may involve reduced insulin action.