Enhancement of genetic instability in human B cells by Epstein-Barr virus latent infection.

The level of genetic instability, as assessed by micronucleus (MN) formation, was higher in Epstein-Barr virus (EBV)-converted B-cell lines with one copy of the EBV genome integrated in each cell than in the parental, EBV-negative, B lymphoma cells. MN induced by EBV latency, as analysed by in situ hybridization, contained mainly centromeric regions, indicating that the presence of EBV affects the segregation of entire chromosomes. The instability was inhibited by treatment with antioxidants. Flow cytometric analysis indicated that there was a higher basal level of peroxides in EBV(+) cells. Direct oxidative stress caused by hydrogen peroxide (which is known to be both apoptogenic and mutagenic) enhanced the number of MN only in an EBV-converted clone. These cells were also resistant to apoptosis, as expected, suggesting that in the parental EBV cells apoptosis may efficiently eliminate cells with genetic damage. These results show for the first time a direct involvement of EBV in the induction of genetic instability, suggesting that it could contribute to tumour progression.