标题：Effects of Obesity on Serum Concentration of Methylation and Oxidative/
Nitrosative Stress Metabolites Following DMBA Treatment of Female
Zucker Rats
摘要：Obesity has been an epidemic in the United States for more than two decades. Studies in humans and animals have suggested that obesity is major risk for breast cancer development. It is well established that increased oxidative stress and changes in DNA methylation can contribute to carcinogenesis. Low molecular weight antioxidant glutathione plays exceptional role in protection of cells from oxidative damage. S-adenosylmethionine, a metabolite of amino acid methionine, is a key methyl group donor for numerous of methylation reaction including DNA. The main objective of this experiment was to investigate the effects of obesity on serum concentration of oxidative stress markers and products of oxidative damage and methylation-reaction donor S-adenosylmethionine following 7,12-dimethylbenz(a) anthracene (DMBA) treatment. Obese and lean female Zucker rats were maintained on a regular chow diet for two weeks. All rats were orally gavaged at age 50 days with 65 mg/kg DMBA. Twenty four hours after DMBA treatment, all rats were sacrificed and serum was collected. Highly sensitive HPLC method with CoulArray electrochemical detector was utilized for determination of thiols, 3-NT and SAM, SAH, and Adenosine. The obese rats had a 40% increased level of oxidized glutathione (P=0.007), decreased GSH/GSSG ratio (P=0.003), increased SAH (P=0.025) and also a 30% increased level of Ado (P=0.005) compared to lean rats. The lean animals showed a slightly higher (20%) concentration of SAM and 50% higher SAM: SAH ratio (P=0.02) compared to obese animals. These results showed that by using DMBA-induced mammary tumor development obesity can contribute to a significant imbalance in oxidative/reduction homeostasis in serum and depression in serum SAM: SAH ratio, known as methylation ratio, and increase SAH level, known as potent inhibitor methylases. These data suggest that changes plasma concentrations of glutathione, SAH and SAM reflect intracellular changes that possibly can contribute to carcinogenesis.
关键词：Obesity; Zucker rats; Oxidative/Nitrosative stress;DMBA-induced mammary tumors; Breast cancer
