Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus X gene transgenic mice.
OBJECTIVE
The preventive effect of interferon (IFN) against hepatocellular carcinoma (HCC) has been confirmed clinically. We sought to determine whether the temporal administration of IFN-beta prevents hepatocarcinogenesis in a mouse model where HCC develops without necroinflammation.


METHODS
Hepatocarcinogenic mice that are transgenic for the hepatitis B virus X gene (HBx-Tg) were treated with IFN-beta or saline (control) for three months, from 3 to 6 months of age, and the incidence of HCC was determined at 18 months of age. The effects of IFN-beta on DNA synthesis and apoptosis were tested.


RESULTS
The incidence of HCC was significantly lower in the IFN-beta-treated mice than the controls (0 vs. 50%, P<0.01). Inhibition of DNA synthesis in hepatocytes by IFN-beta was observed in the livers of HBx-Tg, without any significant induction of apoptosis. Although the treatment of IFN-beta was temporal, the number of hepatocytes with DNA synthesis remained lower 3 and 12 months later in life.


CONCLUSIONS
Temporal administration of IFN-beta has a significant preventive effect on the occurrence of HCC in a mouse model where HCC develops without inflammation. The mechanisms are the inhibition of DNA synthesis and cell cycle progression of hepatocytes.
Yamazaki
Kazuhide
K
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, 1-754, Asahimachi-Dori, Niigata-city 951-8122, Japan.
Suzuki
Kenta
K
Ohkoshi
Shogo
S
Yano
Masahiko
M
Kurita
So
S
Aoki
Yo-Hei
YH
Toba
Ken
K
Takamura
Masa-Aki
MA
Yamagiwa
Satoshi
S
Matsuda
Yasunobu
Y
Aoyagi
Yutaka
Y
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D016196:S Phase / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins
D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016899:Interferon-beta; D004247:DNA