Increased sensitivity of EBNA2-transformed rat fibroblasts to ionizing radiation

To clarify whether expression of Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) correlates with sensitivity to ionizing radiation, we tested EBNA2-transformed rat fibroblast clones for their radiosensitivity to X-rays. These transformed clones reproducibly generated tumors in mice. X-irradiation suppressed the growth of the tumors, and irradiated mice survived longer than non-irradiated ones. In contrast, tumors formed by activated H-ras or E6-E7 genes of human papillomavirus type 16 (HPV16) were strongly resistant to the same dose of X-irradiation. In in vitro culture, these EBNA2-expressing clones also showed higher radiosensitivity than cell lines transformed by activated H-ras and E6-E7 genes. The averaged D_o of EBNA2-expressing clones was 2.3 times lower than that of nonexpressing and control clones. These results suggest that expression EBNA2 is responsible for the radiosensitivity. © 1996 Wiley-Liss, Inc.