Methionine Sulfoxide Stimulates Hepatocarcinogenesis in Non-alcoholic Steatohepatitis (NASH) Mouse: Possible Role of Free Radical-mediated DNA Methylation

Genes and Environment

Toshiyuki Norimura¹  Akira Ootsuyama¹  Hideki Wanibuchi³  Kazuaki Kawai²  Yun-Shan Li²  Anna Kakehashi³  Ming-Fen Song²  Yuko Ootsuyama²  Hiroshi Kasai² 

[1] Department of Radiation Biology, University of Occupational and Environmental Health;Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health;Department of Pathology, Osaka City University Medical School

关键词: methionine sulfoxide (MetO);    DNA methylation;    NASH;    epigenetic;    free radical;   

DOI  :  10.3123/jemsge.34.123

学科分类：分子生物学，细胞生物学和基因

来源: Japanese Environmental Mutagen Society / Nihon Kankyo Hen igen Gakkai

【 摘 要 】

References(33)Cited-By(2)We have reported the formation of 5-methylcytosine from cytosine in vitro, with methyl radicals generated from methionine sulfoxide (MetO). To confirm this reaction in vivo, MetO was added to the drinking water and administered to non-alcoholic steatohepatitis (NASH) mice, which develop hepatitis caused by endogenous oxidative stress. Histopathological examinations revealed incidences of hepatocellular carcinoma of 16.7% and 90% in the 0% and 3% MetO groups, respectively. Higher DNA methylation was detected in the promoter region of the p16 gene isolated from the livers of MetO-treated mice. The higher incidence of liver tumors may be due to the methyl radical-mediated formation of 5-methylcytosine in DNA, which triggers epigenetic changes.

【 授权许可】

Unknown