探討EB 病毒轉活化子Rta 在人類上皮細胞中，促使微核形成、DNA 股斷裂及加速細胞週期M phase進行之研究

Abstract

Epstein-Barr virus（EBV）was the first human DNA virus to be proposed as a tumor virus and EBV infection is associated with the development of many types of malignancies, including nasopharyngeal carcinoma（NPC）. NPC is one of the most common cancer in Taiwan and Southeast China. The cytogenetic studies have demonstrated broad chromosomal abnormalities in NPC tissues. It is suggested that chromosomal instability may play an essential role in the development of NPC, just as in many solid tumors. We investigated whether EBV immediate early gene BRLF1, Rta, contribute to the induction of genomic instability in the human epithelial cells. At first, we demonstrated that EBV Rta could induce micronucleus（MN)formation in 293 inducible stable clone. Secondly, we found EBV Rta accelerates G2/M-to-G1 cell cycle progression in transfected HEp2 cells and HEp2 inducible stable clone. This accelerated cell cycle M phase progression was accompanied with the increase micronuclei formation. Furthermore, we demonstrated that Rta induces DNA strand breaks. However, Rta still enhances the ability of DNA repair in host cell reactivation（HCR）assay. Taken together, these studies suggest that EBV Rta enhances micronucleus formation, DNA strand break and accelerates M phase progression in human epithelial cells.