Effect of soy versus casein protein diet and obesity on S‐adenosylmethionine (SAM), S‐adenosylhomocysteine (SAH) ratio in liver of DMBA‐induced mammary tumor formation in obese Zucker rats

Abstract

Several studies reported that obesity is a major risk factor for breast cancer development and both conditions are associated with disturbances in patterns of DNA methylation. The effects of soy protein diet and obesity on hepatic methylation ratio (SAM:SAH) is unknown. We investigated the effects of long-term soy protein versus casein protein intake and obesity on liver SAM:SAH ratio and induction of mammary tumor in Zucker rats model using DMBA. After one week of acclimation, animals at age of 42 days were randomly assigned to the following 4 diet groups: lean casein, obese casein, lean soy, obese soy. Rats were orally exposed to DMBA (65 mg/kg) at age 50 days and were sacrificed 155 days later. Liver samples were analyzed for SAM and SAH and SAM/SAH ratio using LC-MS technique. Approximately 69% of the lean casein rats developed mammary tumors compared to 50% in lean soy group (p= 0.176). In contrast, 76% of obese soy animals developed mammary tumors compared to 15% (P<0.001) of obese casein. In lean groups, soy-fed rats had higher SAM:SAH ratio (P<0.05) compared to casein-fed. Obese rats on both diets had a significant (P<0.001) increase in SAM:SAH ratio compared to lean rats. In summary, we found that the liver methylation potential (SAM:SAH ratio) can be affected by diet, obesity or their combination and may reflect epigenetic changes in distant organs that modulate the development of tumors. (Supported by USDA and ABI to RH)