细胞色素P450酶系在人鼻咽癌及鼻咽非癌组织中的表达

Expression of Cytochrome P450 Enzymes in Human Nasopharyngeal Carcinoma and Non-cancerous Nasopharynx Tissue

背景与目的:鼻咽癌(nasopharyngealcarcinoma,NPC)的发生与环境及遗传因素密切相关。环境中各种前致癌物需经代谢酶包括细胞色素P450(CytochromeP450,CYP450)的活化才具有致癌作用。本研究拟检测鼻咽癌及鼻咽非癌组织中的CYP450基因表达,以了解与鼻咽部组织中致癌物代谢活化有关的CYP450基因。方法:利用下述两种方法检测CYP450基因的表达:(1)混合7例鼻咽非癌组织的RNA构建cDNA文库,进行克隆测序及生物信息学分析;(2)逆转录14例鼻咽癌组织及8例鼻咽非癌组织的RNA为cDNA,以PCR扩增检测CYP450基因的表达。结果:cDNA文库检测的CYP450基因EST(ExpressedSequenceTag)有CYP1B1、CYP2F1、CYP2J2、CYP4B1、CYP4F12、CYP5A(TBXAS1)、CYP20A1和CYP51A1,其中CYP4B1的EST拷贝数最高,达16个拷贝;RT-PCR检测表达的CYP450基因有CYP1A1、CYP1B1、CYP2A6、CYP2A13、CYP2B6、CYP2C8、CYP2C9、CYP2D6、CYP2E1、CYP2F1、CYP3A4、CYP3A5、CYP3A7、CYP4B1,其中CYP1B1、CYP2B6、CYP4B1已经在文库检测有表达。总共有19个CYP450基因在鼻咽癌及鼻咽非癌组织表达,表达较高的基因有CYP1B1、CYP2C8、CYP2C9、CYP2D6、CYP3A5和CYP4B1。结论:鼻咽部组织表达CYP450基因种类较多,其中包括与前致癌物代谢活化相关的基因。

BACKGROUND &OBJECTIVE: The etiology of nasopharyngeal carcinoma (N PC) is associated with environmental and hereditary factors. Xenobiotics from en vironment must be activated to derive carcinogens. Several cytochrome P450 (CYP4 50) metabolic enzymes participate to the activation of pre-carcinogens, and the genetic polymorphism of those genes is associated with metabolic polymorphism a nd susceptibility to cancer. We performed a preliminary investigation on the xen obiotics metabolism of human nasopharynx by determining the expression of CYP450 genes in NPC and non-cancerous nasopharynx tissues. METHODS: The following two methods were used: (1)A cDNA library from the mixed RNA sample of seven non-ca ncerous nasopharynx tissues was generated, followed by clone sequencing and bioi nformatics analysis. (2)RNA of 14 NPC and 8 non-cancerous nasopharynx tissues w ere reversely transcribed, and the expression of CYP450 genes in those samples w as determined by PCR amplification. RESULTS: Eight ESTs of CYP450 genes includin g CYP1B1, CYP2F1, CYP2J2, CYP4B1, CYP4F12, CYP5A(TBXAS1), CYP20A1, and CYP51A1 w ere detected in non-cancerous nasopharynx cDNA library, among these CYP4B1 exhi bited the highest expression level with 16 copies of ESTs. Positive expression o f fourteen CYP450 genes including CYP1A1, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C 8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP3A4, CYP3A5, CYP3A7, and CYP4B1 were detec ted by RT-PCR, among these, CYP1B1, CYP2B6, and CYP4B1 had also been detected i n the cDNA library. A total of 19 CYP450 genes expression were detected in NPC a nd non-cancerous nasopharynx tissues, and the expression levels of CYP1B1, CYP2 C8, CYP2C9, CYP2D6, CYP3A5, and CYP4B1 were higher than those of the other genes . CONSLUSION: The expression of a great number of CYP450 genes was detected in h uman nasopharynx, some of which might participate to the activation of pre-carc inogen in human nasopharynx. Contribution of these genes to the risk of NPC need s further investigation.