title: Thiamine supplementation attenuated hepatocellular carcinoma in the Atp7b mouse model of Wilson's disease.
abstract: BACKGROUND
  Wilson's disease is caused by a genetic defect in P-type Cu(2+)-ATPase (Atp7b), resulting in Cu(2+) accumulation in the liver, toxicity, and hepatocellular carcinoma. Exposure of HepG2 cells, and livers of Atp7b mutant mice to toxic Cu(2+) resulted in oxidation, (KGDH) and (PDH) enzyme inhibition, and death that was attenuated by thiamine.
  
  
  METHODS
  The effect of oral thiamine supplementation (2%) on hepatocellular carcinoma induced by Cu(2+) accumulation in the livers of Atp7b animals at 4, 6, 9, 12, 16, and 21 months was demonstrated using gross morphology and multi-nucleate analysis.
  
  
  RESULTS
  By 16 months of age, untreated Atp7b animals became moribund, their livers were >180% the weight of controls and >75% of their liver was cancerous. At 16 months the livers of thiamine treated Atp7b mice were <130% the weight of controls and <30% cancerous, and at 21 months the mice were still active. However thiamine was ineffective in a subcutaneous xenograft model.
  
  
  CONCLUSIONS
  This study suggests that thiamine may constitute a prophylactic for Wilson's disease-induced hepatocellular carcinoma.
authors.affiliation: Department of Ophthalmology and the Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, U.S.A. csheli@lsuhsc.edu
authors.forename: Christian T
authors.initials: CT
authors.lastname: Sheline
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D027682:Cation Transport Proteins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000073840:Copper-Transporting ATPases; D019587:Dietary Supplements; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D013831:Thiamine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases; D013831:Thiamine