用原位杂交对树鼩肝组织乙型肝炎病毒DNA定位及其与黄曲霉毒素B_1在肝癌发生中的作用

用生物素标记的HBV DNA探针对经83～158周实验的55只树鼩肝组织的福尔马林固定、石蜡包埋的切片进行原位分子杂交研究。在45只接种过人HBV的树鼩中,有30只在肝细胞检出HBV DNA。这55只树鼩,有41只摄入了AFB_1,其中肝细胞HBV DNA阳性的A组22只,有10只发生了HCC;19只HBVDNA阴性的B组,只发生2例HCC,两组差别显著(P<0.05)。未接触过AFB_1的14只树鼩中,肝细胞HBVDNA阳性的8只(C组),发生1例HCC;而HBV DNA阴性的6只(D组)无HCC发生。提示HBV和AFB_1在诱发树鼩HCC中起协同作用;并支持HBV感染与HCC存在病因学关系的观点。该实验HBV DNA阳性物质主要分布于癌外肝细胞胞浆内,少数位于肝细胞核。癌组织内HBV DNA阳性率低于癌外肝组织。与在人肝癌研究的结果一致。表明树鼩是研究HBV致癌分子机理的较好的模型。

A STUDY ON THE DISTRIBUTION OF HEPATITIS B VIRUS DNA IN LIVER CANCER AND THE RELATIONSHIP WITH LIVER CANCER IN TREE SHREWS BY IN SITU HYBRIDIZATION

The authors investigated the hepatocytic status of HBV DNA in the liver andcancer tissues of tree shrews inoculated with human hepatitis B virus (HHBV). and the effects of HHBV and aflatoxin B_1 (AFB_1) in the development of primary livercancer (PLC) by in situ hybridization on formalin-fixed sections with biotin-labelledprobe. 11 cases of PLC were developed in 30 tree shrews which were positive for HBVDNA in the liver cells HBV DNA distributed in cancer cell cytoplasm in 3 of 5 animals,and in the nuclei in the rest 2. HBV DNA appeared under the eellular membranesand in the nuclei of hepatocytes outside the liver cancer. Among the tree shrewsadministered with AFB_1 the incidence of HCC was 45.45% in HBV DNA positiveanimals and was 10.5% in those negative ones. In 14 tree shrews not exposed toAFB_1, 1/8 of HBV DNA positive ones developed HCC, and no HCC was found in the6 negative animals. These results show that HBV and AFB_1 have synergistic effectsin the development of experimental HCC.