癌变·畸变·突变 ›› 2005, Vol. 17 ›› Issue (3): 152-155.doi: 10.3969/j.issn.1004-616x.2005.03.007

• 论著 • 上一篇    下一篇

CYP2D家族基因在大鼠肝癌组织中的表达及突变研究

宁 宗;赵晓琴;王乃平   

  1. 广西医科大学第一附属医院急诊科, 广西南宁 530021
  • 收稿日期:2004-08-16 修回日期:2004-10-12 出版日期:2005-05-30 发布日期:2005-05-30
  • 通讯作者: 宁 宗

Expression and Mutation Analysis of CYP2D Subfamily Gene in Rat Hepatocarcinoma

NING Zong;ZHAO Xiao-qin;WANG Nai-ping   

  1. The First Affiliated Hospital of Guangxi Medical University,Nanning,530021,Guangxi,China
  • Received:2004-08-16 Revised:2004-10-12 Online:2005-05-30 Published:2005-05-30
  • Contact: NING Zong

摘要: 背景与目的: 观察二甲氨基偶氮苯(Dimethylaminoazobenzene,DAB)诱导大鼠形成肝癌后细胞色素CYP2D家族基因的表达水平及突变并分析其意义。 材料与方法: 用DAB诱导大鼠形成肝癌,RT-PCR定量分析CYP2D1、CYP2D2和CYP2D4 mRNA在肝脏中的表达水平,并对各PCR产物测序分析,观察是否有点突变。 结果: CYP2D2和CYP2D4 的mRNA表达水平在肝脏癌组织中及癌旁组织中明显低于正常组织,两者在癌组织中的表达水平低于在癌旁组织;CYP2D1在肝脏癌组织中及癌旁组织中的的表达水平虽低于正常组织,但之间无明显的差异性。CYP2D2在肝脏癌组织的PCR产物经测序分析存在碱基插入突变。 结论: DAB可以不同程度降低CYP2D家族基因在肝脏的表达,并可以诱发CYP2D2基因点突变,CYP2D家族基因差异性与肝癌形成有密切关系。

关键词: 二甲氨基偶氮苯, 肝癌, CYP2D1基因, CYP2D2基因, CYP2D4基因, 突变

Abstract: BACKGROUND & AIM: To analyze the expressions and their sequences of cytochrome P4502D(CYP2D) subfamily gene in rat heptocarcinoma induced by dimethylaminoazobenzene(DAB). MATERIAL AND METHODS: The rats were induced by azo dye DAB ,the mRNA expression of three isoforms(CYP2D1、CYP2D2 and CYP2D4)were detected by quantitative RT-PCR,then PCR products were sequenced and analyzed. RESULTS: The expression in CYP2D2 and CYP2D4 mRNA decreased dramatically both in hepatocarcinoma and paracancerous tissues(P<0.01),and mRNA of the two isoforms in hepatocarcinoma tissues was lower than in paracancerous tissues(P<0.01). Though CYP2D1 mRNA had a trend of decrease in hepatocarcinoma and paracancerous tissues, no significant difference was found between them. Sequence analysis of those PCR products showed that only a single-site base mutation happened in CYP2D2 from hepatocarcinoma tissues. CONCLUSION: the expression of three isoforms(CYP2D1,CYP2D2 and CYP2D4) mRNA were reduced differently by oza dye DAB, DAB could result in CYP2D2 gene mutation, these indicate that the variants of CYP2D genes may contribute to the progression of hepatocarcinoma.   

Key words: dimethylaminoazobenzene, hepatocarcinoma, CYP2D1 gene, CYP2D2 gene, CYP2D4 gene, mutation