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Deletion of integrated hepatitis B virus genome and cellular flanking sequences in hepatocellular carcinoma cells in BALB/c Mice

✍ Scribed by Poa-Chun Chang; Cheng-Po Hu; Shu-Hsia Chen; Sheng Wang-Wuu; Chungming Chang

Publisher: John Wiley and Sons
Year: 1995
Tongue: English
Weight: 663 KB
Volume: 21
Category: Article
ISSN: 0270-9139
DOI: 10.1002/hep.1840210605

No coin nor oath required. For personal study only.

✦ Synopsis

We have previously reported the establishment of well-differentiated BALB/c mouse liver (ML) cell lines. Transfection of these cell lines with hepatitis B virus (HBV) DNA led to the expression of HBV-specific antigens and integration of HBV sequences in the cellular genome. Two cloned HBV-transfected ML cell lines, ML-2(HBV) and ML,-3(HBV), expressed viral antigens and were highly tumorigenic in nude mice. However, the tumorigenicity of the two cell lines was significantly reduced in BALBk mice. Southern blot analyses showed that the integrated HBV sequences were retained in tumors growing in nude mice but deleted in tumors growing in BALB/c mice. Furthermore, the deletion of HBV DNA was accompanied by deletion of chromosomal sequences flanking the HBV integration sites. In ML-2(HBV) cells, a significant reduction in chromosomal number was also observed. These results suggest that the immune response of BALB/c mice selected against hepatocellular carcinoma (HCC) cells expressing viral antigens and led to the proliferation of cells with deleted HBV sequences and concomitant chromosome aberrations. By using this mechanism, HCC cells escape the immune surveillance and gain the advantage of cell growth. (HEPATOLOGY 1995;21:1504-1509.)

The development of malignant neoplasm proceeds through multiple stages, including initiation, promotion, and progression. Environmental mutagens, viral infections, and endogenous cellular factors play key roles during the initiation and transition of these stages.' Causative studies have shown a close relationship between the chronic hepatitis B virus (HBV) infec-Abbreviations: HRV, hepatitis I3 virus; HCC, hepatocellular carcinoma; ML, mouse liver; HBsAg, hepatitis B surface antigen; HBcieAg, hepatitis B cie antigen , From the ' Graduate

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