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

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 which is more resistant to AOM-induced DNA damage and which may involve reduced insulin action. Supported by USDA 6251-51000-004-01S.