HERPES-SIMPLEX VIRUS THYMIDINE KINASE GANCICLOVIR-MEDIATED APOPTOTIC DEATH OF BYSTANDER CELLS/

An emerging strategy for cancer gene therapy involves the transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cel ls, rendering them susceptible to the cytotoxic effects of ganciclovir . The observation that HSV-tk-expressing cells can also induce cell de ath in neighboring cells, which do not express HSV-tk, has been called the bystander effect, Gap junction-mediated transfer of cytotoxic mol ecules to bystander cells may be an important mechanism of bystander c ell death, although others have suggested a role for phagocytosis. In this study, we evaluated the mode of cell death in bystander cells, We detected apoptosis in bystander cells and found that bystander cell d eath could be inhibited by BCL2 expression. We determined that gancicl ovir incubations for 10 h were sufficient to induce cell death in most bystander cells cocultured with HSV-tk-expressing cells, During this period, no phagocytosis was detected, although it was obvious at later stages.