Zhai W R, Vajta G, Acs G, Paronetto F
Immunopathology Laboratory, Veterans Administration Medical Center, New York, New York.
Gastroenterology. 1990 Feb;98(2):470-7. doi: 10.1016/0016-5085(90)90840-w.
Hepatitis B virus genome-transfected HepG2 cells (2.2.15 cells) inoculated into nude mice produced tumors within 2-8 wk. Dane particles, hepatitis B virus deoxyribonucleic acid polymerase activity, hepatitis B surface antigen, and hepatitis B e antigen were detected in the serum, and 36% of mice developed antibodies to hepatitis B core antigen. In the tumors, hepatitis B surface, core, and e antigens were observed by electron microscopy and immunoenzymatic techniques. In-situ hybridization and Southern blot analysis showed hepatitis B virus deoxyribonucleic acid in the tumor. Tumors could be propagated by injection of minced tumor tissue or of a tumor-derived cell line. Liver of tumor-bearing mice as well as sera and tissues of mice inoculated with control cell lines did not show hepatitis B virus genome or viral markers. Tumors induced by both 2.2.15 and nontransfected HepG2 cells exhibited myc oncogene protein and various hepatoma-associated antigens (alpha-fetoprotein, alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen, cytokeratin), suggesting that viral formation does not interfere with expression of these antigens. This experimental model will be helpful to study the effect of drugs on in-vivo hepatitis B virus replication and viral antigen expression.
将乙肝病毒基因组转染的HepG2细胞（2.2.15细胞）接种到裸鼠体内，2 - 8周内产生了肿瘤。在血清中检测到了 Dane颗粒、乙肝病毒脱氧核糖核酸聚合酶活性、乙肝表面抗原和乙肝e抗原，36%的小鼠产生了针对乙肝核心抗原的抗体。通过电子显微镜和免疫酶技术在肿瘤中观察到了乙肝表面、核心和e抗原。原位杂交和Southern印迹分析显示肿瘤中有乙肝病毒脱氧核糖核酸。肿瘤可以通过注射切碎的肿瘤组织或肿瘤衍生的细胞系进行传代。接种对照细胞系的小鼠的肝脏以及血清和组织未显示乙肝病毒基因组或病毒标志物。2.2.15细胞和未转染的HepG2细胞诱导的肿瘤均表现出myc癌基因蛋白和各种肝癌相关抗原（甲胎蛋白、α1 -抗胰蛋白酶、α1 -抗糜蛋白酶、癌胚抗原、细胞角蛋白），表明病毒形成并不干扰这些抗原的表达。该实验模型将有助于研究药物对体内乙肝病毒复制和病毒抗原表达的影响。
