title: Preliminary results of interferon-alpha therapy on woodchuck hepatitis virus-induced hepatocarcinogenesis: possible benefit in female transgenic mice.
abstract: BACKGROUND
  C-myc activation is a potent oncogenic event in hepatocarcinogenesis. The aim of this study was to test the preventive effect of interferon-alpha (IFN-alpha) on the development of dysplasia and subsequent hepatocellular carcinoma (HCC) in transgenic (Tg) mice overexpressing c-myc in the liver.
  
  
  METHODS
  The WHV/c-myc Tg mice recapitulating woodchuck hepatitis virus-induced hepatocarcinogenesis were treated with IFN-alpha, starting early in life until sacrifice at pre-neoplastic or neoplastic stages. Transgene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), hepatocyte proliferation was assessed by bromodeoxyuridine incorporation and RT-PCR for proliferating cell nuclear antigen, and apoptosis was assessed by in situ nick-end-labeling of DNA.
  
  
  RESULTS
  C-myc expression and hepatocyte proliferation were significantly reduced in treated female mice, without modification of apoptosis, correlating with a lower severity of dysplasia in 9/12 treated animals at pre-neoplastic stages. At the neoplastic stage, 2/3 treated females neither exhibited carcinoma nor dysplasia, while all 6/6 untreated mice and 3/3 treated males developed carcinomas.
  
  
  CONCLUSIONS
  Inhibition of c-myc and hepatocyte proliferation by long-term administration of IFN-alpha was associated with a decrease, or a delay, of oncogenesis in the mouse Tg HCC model. Whether c-myc and hepatocyte proliferation down-regulation could be relevant parameters of IFN-alpha efficiency for hepatocarcinogenesis prevention in cirrhotic patients should be established.
authors.affiliation: INSERM Unit 271, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Merle
authors.forename: M
authors.initials: M
authors.lastname: Chevallier
authors.forename: R
authors.initials: R
authors.lastname: Levy
authors.forename: M
authors.initials: M
authors.lastname: Maisonnas
authors.forename: O
authors.initials: O
authors.lastname: Terradillos
authors.lastname: Ahmed SNS
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: M A
authors.initials: MA
authors.lastname: Buendia
authors.forename: L
authors.initials: L
authors.lastname: Vitvitski-Trépo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D017919:Hepatitis B Virus, Woodchuck; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D016898:Interferon-alpha; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins