[Efficacy of interferon alpha in primary prevention of preneoplastic lesions in a transgenic murine model of hepatocellular carcinoma related to the interaction between woodchuck hepatitis viruses and c-myc oncogene].
OBJECTIVE
C-myc oncogene overexpression by near insertion of hepatitis B virus is important in woodchuck hepatocarcinogenesis. This DNA fragment was transferred in mice who developed hepatocellular carcinoma via preneoplastic lesions. In the present study, we tested the preventive effect of alpha interferon on the incidence of hepatocyte dysplasia.


METHODS
Human recombinant alpha interferon hybrid B/D was continuously administered at increasing doses (0 to 10,000 IU/g) in a transgenic mouse model. One cohort was treated from day 21 to day 80. A histological liver examination was performed and the transgene expression was assessed by hybridization with or without previous genic amplification, and by indirect immunofluorescence.


RESULTS
At day 15, histological liver examination was normal. Interferon treatment decreased the expression of viral sequences, but not of c-myc. At day 80, interferon treatment resulted in a reduction of the incidence and severity of dysplasic lesions, and a marked decrease in c-myc overexpression.


CONCLUSIONS
In this transgenic mouse model, alpha interferon treatment decreased the incidence and severity of precancerous lesions, due to a reduction in c-myc overexpression. This prophylaxis could be of interest in human hepatocarcinogenesis where c-myc overexpression is frequent.
Merle
P
P
Laboratoire de Recherche sur les Hépatites et les Rétrovirus Humains, INSERM U271, Lyon.
Levy
R
R
Vitvitski
L
L
Chevallier
M
M
Buendia
M A
MA
Trepo
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D017919:Hepatitis B Virus, Woodchuck / Q000502:physiology; D006520:Hepatitis, Animal / Q000235:genetics / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes / Q000502:physiology; D011230:Precancerous Conditions / Q000235:genetics / Q000517:prevention & control*; D013997:Time Factors; D019076:Transgenes / Q000502:physiology
D000970:Antineoplastic Agents; D016898:Interferon-alpha