Background & objective: The etiology of nasopharyngeal carcinoma (NPC) is associated with environmental and hereditary factors. Xenobiotics from environment must be activated to derive carcinogens. Several cytochrome P450 (CYP450) metabolic enzymes participate to the activation of pre-carcinogens, and the genetic polymorphism of those genes is associated with metabolic polymorphism and susceptibility to cancer. We performed a preliminary investigation on the xenobiotics 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-cancerous nasopharynx tissues was generated, followed by clone sequencing and bioinformatics analysis. (2)RNA of 14 NPC and 8 non-cancerous nasopharynx tissues were reversely transcribed, and the expression of CYP450 genes in those samples was determined by PCR amplification.
Results: Eight ESTs of CYP450 genes including CYP1B1, CYP2F1, CYP2J2, CYP4B1, CYP4F12, CYP5A(TBXAS1), CYP20A1, and CYP51A1 were detected in non-cancerous nasopharynx cDNA library, among these CYP4B1 exhibited the highest expression level with 16 copies of ESTs. Positive expression of fourteen CYP450 genes including CYP1A1, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP2F1, CYP3A4, CYP3A5, CYP3A7, and CYP4B1 were detected by RT-PCR, among these, CYP1B1, CYP2B6, and CYP4B1 had also been detected in the cDNA library. A total of 19 CYP450 genes expression were detected in NPC and non-cancerous nasopharynx tissues, and the expression levels of CYP1B1, CYP2C8, CYP2C9, CYP2D6, CYP3A5, and CYP4B1 were higher than those of the other genes.
Conclusion: The expression of a great number of CYP450 genes was detected in human nasopharynx, some of which might participate to the activation of pre-carcinogen in human nasopharynx. Contribution of these genes to the risk of NPC needs further investigation.