Abstract 740: Obesity promotes liver pro-oxidative and DNA damage in mammary tumor of Zucker rats

Abstract Obesity is a major health problem in the US and world. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, and certain types of cancers such as breast cancer. Our laboratory reported that obesity increased mammary tumor model using obese Zucker rat model. However, the effects of obesity in the liver in regard to oxidative stress and DNA reaction is less known. In present study, we used a DMBA induced-mammary tumor model to further investigate the effects of obesity on creation of pro-oxidative environment in liver and oxidative DNA reaction. Lean and obese female rats were at 50 days of age received 7,12-dimethylbenz(α)anthracene (DMBA) and were sacrificed 20 weeks later. HPLC-ECD, HPLC-UV and LC-MS were used. Obesity capable significantly modify methylation status in liver caused higher (p < 0.001) SAM/SAH ratio (know as “methylation ratio”) and increased (p < 0.05) global DNA methylation. Also, obesity decrease GSH/GSSG ratio (known as “oxidative stress ratio”) with p < 0.0001 inducing higher oxidative stress and as results, increase presence both oxidized guanosine (8-OH-Guanosine) with p < 0.001 and oxidized 5metylCytosine (5hmCytosine) p<0.04 in liver DNA. 8-OH-Guanosine/5hmCytosine ratio was not significantly affected. Obesity caused significant oxidative stress in liver, causing oxidative DNA damage and change of DNA methylation pattern. These changes may contribute to the development of fatty liver in breast cancer models. Citation Format: Reza Hakkak, Stepan Melnyk, Soheila Korourian. Obesity promotes liver pro-oxidative and DNA damage in mammary tumor of Zucker rats [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 740.