Abstract 3460: Effects of feeding soy protein isolate diet on hepatic methylation and oxidative stress in DMBA-induced mammary tumor in obese rat model

Abstract

Abstract The obesity epidemic is in the United States and world for past two decades. There is a link between obesity and chronic diseases development such as diabetes, cardiovascular disease and certain types of cancers including breast cancer. Obesity has a significant impact on the metabolic profiles for a variety of cellular-tissue-organ levels in animals and humans. The objective of this study was to determine the effects of obesity and a soy protein isolate (SPI) diet on liver methylation and oxidative stress using 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumor model. We hypothesize that SPI diet is capable to reduce the liver damage by reducing oxidative stress and modifying methylation status. After one week of acclimation, five weeks old female lean and obese Zucker rats were randomly fed AIN-93-G diet with either casein (CAS as control) or SPI as source of protein. All rats were orally gavaged at age 50 days with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly and sacrificed 22 weeks post-DMBA treatment. Liver sample metabolites concentrations were measured using HPLC with Electrochemical Detection and LC-MS. Our results shows that: 1) Obesity increased significantly (P<0.001) body weight for both CAS and SPI diets; 2) 69% of the Lean casein rats developed mammary tumors compared to 50% in lean soy group (p= 0.176) and in the obese group, 76% of the soy-fed rats developed mammary tumors compared to 15% (P<0.001) of obese casein- fed rats; 4) Obesity in both diets significantly modify liver methylation and oxidative stress status; 5) lean SPI-fed rats significantly (P<0.025) increased SAM/SAH “methylation ratio” compare to lean CAS-fed rats; 6) obese SPI-fed rats significantly (P<0.001) decrease level of Homocysteine in liver and increase significantly (P<0.001) Methionine/Homocysteine ratio compared CAS obese rats; 7) obesity caused a significant increase in oxidative stress (GSH/GSSG ratio decrease) in liver for both CAS (P<0.004) and SPI (P<0.01) diets and 8) obese SPI fed rats significantly (P<0.02) decreased oxidative in liver (GSH/GSSG ratio increase) compared to obese CAS fed rats. In summary, we found that SPI diet capable make significant impact on methylation status by increasing a “methylation ratio”, decrease level of toxic intracellular compound homocysteine, and improving redox environment in liver triggered by obesity in mammary tumor model. Citation Format: Reza Hakkak, Stepan Melnyk, Soheila Korourian. Effects of feeding soy protein isolate diet on hepatic methylation and oxidative stress in DMBA-induced mammary tumor in obese rat model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3460.