Glycine N-methyltransferase affects the metabolism of aflatoxin B1 and blocks its carcinogenic effect

Toxicology and Applied Pharmacology
Chia-Hung YenYi-Ming Arthur Chen

Abstract

Previously, we reported that glycine N-methyltransferase (GNMT) knockout mice develop chronic hepatitis and hepatocellular carcinoma (HCC) spontaneously. For this study we used a phosphoenolpyruvate carboxykinase promoter to establish a GNMT transgenic (TG) mouse model. Animals were intraperitoneally inoculated with aflatoxin B(1) (AFB(1)) and monitored for 11 months, during which neither male nor female GNMT-TG mice developed HCC. In contrast, 4 of 6 (67%) male wild-type mice developed HCC. Immunofluorescent antibody test showed that GNMT was translocated into nuclei after AFB(1) treatment. Competitive enzyme immunoassays indicated that after AFB(1) treatment, the AFB(1)-DNA adducts formed in stable clones expressing GNMT reduced 51.4% compared to the vector control clones. Experiments using recombinant adenoviruses carrying GNMT cDNA (Ad-GNMT) further demonstrated that the GNMT-related inhibition of AFB(1)-DNA adducts formation is dose-dependent. HPLC analysis of the metabolites of AFB(1) in the cultural supernatants of cells exposed to AFB(1) showed that the AFM(1) level in the GNMT group was significantly higher than the control group, indicating the presence of GNMT can enhance the detoxification pathway of AFB(1). Cytotox...Continue Reading

Citations

Oct 8, 2013·International Journal of Hygiene and Environmental Health·S Mohd RedzwanAhmad Zuraini
Nov 14, 2012·Toxicology and Applied Pharmacology·Chia-Hung YenYi-Ming Arthur Chen
May 18, 2010·International Journal of Cancer. Journal International Du Cancer·Shih-Ping LiuYi-Ming Arthur Chen
Dec 8, 2010·Proteomics. Clinical Applications·Yi-Jen LiaoYi-Ming Arthur Chen
Aug 8, 2013·International Journal of Cancer. Journal International Du Cancer·Yi-Cheng WangEn-Pei Isabel Chiang
Nov 6, 2009·The International Journal of Neuropsychopharmacology·Hsien-Yuan LaneGuochuan E Tsai
Jun 22, 2011·Journal of Occupational and Environmental Medicine·Marcelo ChenYi-Ming Arthur Chen
Aug 18, 2018·Scientific Reports·Jung-Hsien HungYi-Ming Arthur Chen
Jun 7, 2019·Toxicology and Applied Pharmacology·Marcelo ChenYi-Ming Arthur Chen
Aug 22, 2021·Toxicology and Applied Pharmacology·Wei ZhangAi Gao

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