外遺傳機制，藉由去氧核醣核酸或組蛋白的修飾，導致基因可遺傳的抑制或活化作用，而這個機制不會改變去氧核醣核酸序列。最近研究顯示去氧核醣核酸的甲基化對於惡性腫瘤的形成扮演重要角色，包括在腫瘤抑制基因過度甲基或在致癌基因的低甲基化。Epstein-Barr病毒(EB病毒)是一種γ皰疹病毒，超過90%人口都被傳染，但是多數被感染的人依然是無任何症狀的。早先研究指出，EB病毒和許多人類的惡性腫瘤相關，譬如鼻咽癌、伯奇氏淋巴瘤(Burkitt’s lymphoma)，T細胞淋巴瘤，和NK/T細胞淋巴瘤等。在之前的研究雖有報導在被EB病毒傳染的細胞，或轉殖EB病毒致癌蛋白LMP1(潛伏膜蛋白1)的細胞裡去氧核醣核酸甲基化的情形被改變；但是,對於EB病毒感染細胞後，是否會藉著改變宿主基因體中去氧核醣核酸甲基化的情形，而導致腫瘤的發展，仍然是不清楚的。這個研究的目的是調查在被EB病毒感染的細胞，或轉殖EB病毒致癌蛋白LMP1(潛伏膜蛋白1)的淋巴瘤細胞基因體中去氧核醣核酸的甲基化情形。我們先檢驗不同的淋巴瘤細胞株中被EB病毒感染的狀態和細胞中基因體去氧核醣核酸的甲基化樣式的關係。並利用南方墨點轉漬法以及西部墨點轉漬法分析這些淋巴瘤細胞的整體去氧核醣核酸甲基化的水平。此外，再分析轉殖EB病毒致癌蛋白LMP1 (潛伏膜蛋白1)的BJAB 和H9細胞株中 (BJAB-LMP1, H9-LMP1)。我們也利用相同的工具來研究細胞，整體去氧核醣核酸甲基化狀態。在第一部分的實驗中發現，被EB病毒感染的細胞株，Raji細胞在甲基化水平上和其他細胞相比並沒有特別出入；在去氧核醣核酸甲基轉化酶3a、3b的表現量比其他B細胞低，而去氧核醣核酸甲基轉化酶1的表現量比其他B細胞高。此外，去氧核醣核酸甲基轉化酶的表現量和細胞中去氧核醣核酸的甲基化程度是因著不同細胞而不同的，且三種去氧核醣核酸甲基轉化酶的表現量似乎是獨立的。在LMP1對細胞的影響方面，從我們的實驗結果發現，H9和H9-LMP1細胞的去氧核醣核酸甲基轉化酶1, 3a, 3b (DNMT1, 3a, 3b)的表現量是沒有差異的。然而，在BJAB 和BJAB-LMP1 細胞中，去氧核醣核酸甲基轉化酶3a, 3b (DNMT3a, 3b)有相似的表現量,但是在DNMT1的表現量上，BJAB細胞比BJAB-LMP1細胞能表達較多的DNMT1蛋白質。另外,我們的數據指出正常B和T細胞的基因體相較於BJAB和H9細胞以及BJAB-LMP1和H9-LMP1細胞而言，是過甲基化的。另外，BJAB 和BJAB-LMP1細胞由於在甲基化水平上是沒有區別的，但是H9-LMP1細胞相對H9細胞而言是低甲基化的，此結果也暗示LMP1的影響似乎在不同細胞種類視線不相同的。

Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing or activation of genes without a change in their sequences. Recent studies revealed DNA methylation contributing to the malignancy that may be involved hypermethylation in tumor suppressor genes or hypomethylation in oncogenes. Epstein-Barr virus (EBV) is a γ herpesvirus that infects more than 90% of the human population, although the majority of carriers remain asymptomatic. Previous studies indicated that EBV is associated with many human malignancies such as nasopharyngeal carcinoma, Burkitt’s lymphoma, T cell lymphoma, and natural killer (NK)/T cell lymphoma. Altered methylation pattern in EBV-infected or EBV oncoprotein LMP1-transfected cells have been reported in some tumors; however, it remains unclear whether EBV infection changes methylation pattern in the host genome that leads to the development of tumor. This study aims to investigate genomic methylation pattern in EBV-infected or EBV oncoprotein LMP1-transfected lymphoma cells. We have assayed EBV-infected status with genomic methylation pattern in various lymphoma cell lines. The global methylation levels of these lymphoma cells were determined by Southern blot analysis against human repetitive sequences and Western blot analysis with antibodies against DNA methyltransferases (DNMTs). Furthermore, the global methylation status in BJAB and H9 cells transfected with LMP1 were determined by the same approaches. Among three B lymphoma cell lines, the EBV infected Raji cells have the highest expression level of DNMT1 and lowest expression of DNMT3a and 3b. Furthermore, the expression levels of DNMTs and DNA methylation are different in various lymphoma cell lines. The expression patterns of the three DNMTs in different cell lines seem to be independent. There is no difference between H9 and H9-LMP1 cells in expression levels of DNMT1, 3a, 3b. BJAB and BJAB-LMP1 cells have similar expression levels of DNMT3a and DNMT3b, but BJAB cells express more DNMT1 protein than BJAB-LMP1 cells (P<0.05.) In addition, our data indicated the normal B and T cells are hypermethylated in comparison with BJAB and H9 lymphoma alone or transfected with LMP1. BJAB and BJAB-LMP1 cells have no difference in methylation level. H9-LMP1 is more hypomethylated than H9. These results suggest the effects of LMP1 transfection are distinct in different cell types.

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