树鼩实验性肝癌发生过程p53基因的变化  

Alteration of p53 gene during tree shrews'hepatocarcinogenesis

作　　者：苏建家[1] 李瑗[1] 班克臣[1] 覃柳亮[1] 王辉云[2] 杨春[1] 欧超[1] 段小娴 李永翊 严瑞琪[2] 

机构地区：[1]广西肿瘤防治研究所,530021 [2]中山医科大学肿瘤研究所病理研究室 [3]韩国生物科学及生物技术研究所韩国癌症研究部

出　　处：《中华肝脏病杂志》2003年第3期159-161,共3页Chinese Journal of Hepatology

基　　金：国家自然科学基金(39260033);广西桂科基(0143058)

摘　　要：目的 探讨由人乙型肝炎病毒(HBV)和黄曲霉毒索B1(AFB1)诱发的树鼩肝细胞癌变过程,p53基因的表达及变化。方法 将树鼩分为四组:A组:HBV+AFB1;B组:只感染HBV;c组:只摄入AFB1;D组:作空白对照。定期肝活检,用免疫组织化学、分子生物学等技术对实验树鼩肝及肿瘤组织进行检测。 结果 (1)接受HBV及AFB1双因素的A组,肝细胞癌(HCC)发生率(66.7％)明显高于只接受HBV的B组或AFB1的C组(30％),而且HCC的平均发生时间也明显早于C组,(120.0±16.6)周与(153.3±5.8)周,t=3.336,P<0.01。(2)在第75周前各组动物肝均未检出突变的p53蛋白。(3)105周时,A组p53蛋白表达率为78.6％,B组为60％,C组为71.4％,D组为10％(x2≥5.03,P<0.05)。在A、C组检出p53基因异常带。(4)树鼩肝癌p53基因突变点分别位于275、78及13密码子;其野生型p53基因的核苷酸及氨基酸序列与人的p53基因的核苷酸及氨基酸序列的同源性分别为91.7％、93.4％。 结论 再次证实HBV和AFB1有协同致肝癌作用;突变的p53蛋白出现于肝细胞发生癌变之前,p53基因的突变促进了肝癌的发生和演进。HBV可能协同AFB1致p53基因突变。Objective To detect the expression and variation of p53 gene during tree shrews' hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin Bl (AFB1). Methods Tree shrews were divided into four groups: the tree shrews were infected with HBV and fed with AFB1 in group A, only infected with HBV in group B, fed with AFB1 alone in group C, and normal control in group D. All the tree shrews were performed liver biopsy every 15 weeks. The tissues of liver and tumor were detected by immunohistochemistry and molecular biotechnologies. Results (1) The incidence of hepatocellular carcinoma (HCC) in group A (66.7%) was higher than that in Group B and C (30%). HCC appearance in group A was earlier than that in group C (120.0 weeks ± 16.6 weeks vs 153.3 weeks±5.8 weeks, t = 3.336, P < 0.01). (2) Mutated p53 protein was not found before the 75th week of the experiment in each group. (3) At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60% and 71.4% in group A, B and C respectively, which were much higher than that (10%) in group D ( x2≥5.03, P < 0.05). An abnormal band of p53 gene was detected in both group A and C. (4) The mutation points of p53 gene in liver cancer of tree shrew were at codon 275, 78 and 13. The nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homology with those of human p53 respectively. Conclusions There is a remarkable synergistic effect between HBV and AFB1 on HCC. Mutated p53 protein is expressed before HCC occurrence, which promotes the development and progress of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.

关 键 词：树QU 实验性肝癌 发生过程 P53基因 黄曲霉毒素 

分 类 号：R735.7[医药卫生—肿瘤]