'Bystander killing' induces apoptosis and is inhibited by forskolin

'Bystander killing' is a term used to describe the broad cell death associated with the transduction of the herpes simplex virus thymidine kinase gene (HSV1-tk) and administration of nucleoside analogs and which extends the killing effect to adjacent cells not transduced with HSV1-tk ('bystander cells'). HSV1-tk negative cells can be killed by co-culture with HSV1-tk positive cells at a ratio as small as one HSV1-tk positive to 32 HSV1-tk negative cells (1:32). In this report, several aspects of bystander killing are characterized. First, the sensitivity to bystander killing is shown to differ among cell lines. Second, cell-to-cell contact, or at least proximity between cells, is demonstrated to be necessary for bystander killing. Third, forskolin is shown to inhibit bystander killing. We also show that bystander killing is not species specific. Finally, it is demonstrated that cell death induced by bystander killing is mediated via apoptosis.