EBV Conference 2008 Guangzhou - Baylor College of Medicine

179 (RegID: 1503; 1504; 1506; 1507; 1510)
Chih-Yeu Fang
Institution: National Cancer Research Institute, National Health Research Institutes, Taiwan
e-mail: cyf@nhri.org.tw
RECURRENT CHEMICAL REACTIVATIONS OF EBV PROMOTES GENOME INSTABILITY
AND CHROMOSOMAL ABERRATIONS OF NASOPHARYNGEAL CARCINOMA CELLS
Chih-Yeu Fang(1), Chia-Huei Lee(1), Chung-Chun Wu(1), Yu-Ting Chang(1), Shu-Ling Yu(1),
Sheng-Ping Chou(1), Ping-Ting Huang(2), Chi-Long Chen(3), Jia-Woei Hou(4), Yao Chang(5),
Ching-Hwa Tsai(3), Kenzo Takada(6) and Jen-Yang Chen(1,2)
Abstract:
Nasopharyngeal carcinoma (NPC) is an endemic malignancy prevalent in southern Chinese males.
Epidemiological studies have associated this disease closely with Epstein-Barr virus (EBV) infection. It
also has been proposed that chemicals in herbal medicines or diet may induce EBV reactivation and lead
to NPC. Because of the lack of an appropriate model system, this hypothesis has not been seriously tested
and the mechanism has not been elucidated. Genomic instability is considered to contribute to the
development of human cancers and has been found to occur in many NPCs. Therefore, in this study, we
tried to elucidate whether EBV reactivation by chemicals promotes genomic instability of NPC cells. NPC
cell lines latently infected with EBV, NA and HA, and the corresponding EBV-negative NPC cell lines,
NPC-TW01 (TW01) and HONE-1, were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and
sodium n-butyrate (SB). Increases in genomic instability were determined by the formation of micronuclei
(MN). Double strand breaks (DSB) in DNA were detected by g-H2AX staining. A single treatment with
TPA/SB revealed that formation of MN increased in NA and HA cells but not in TW01 and HONE-1 cells.
However, 15 recurrent reactivations of EBV in NA and HA cells resulted in a marked increase in the
accumulation of genomic instability, as revealed by the formation of MN and chromosomal aberrations.
Transwell assay of TW01 and NA cells revealed a profound increase in the invasiveness of the repeatedly
reactivated NA cells but not TW01 cells. These data show that EBV reactivations may result in DNA
damage and consequent genomic instability. With recurrent reactivations these effects accumulate and
may lead to a more malignant phenotype of NPC.
EBV Conference 2008 Guangzhou
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