Cyclosporin a inhibits 2-chloroadenosine-induced DNA cleavage in mouse thymocytes

Incubation of mouse thymocytes with the adenosine analogue 2-chloroadenosine resulted in enhanced internucleosomal DNA fragmentation which could be inhibited by the immunosuppressive drug cyclosporin A. In order to be effective, cyclosporin A had to be added to thymocyte preparations at the same time as 2-chloroadenosine. Since cyclosporin A is a selective inhibitor of calcineurin, our data suggest a possible role for calcineurin as a signaling intermediate in the apoptotic pathway activated in thymocytes through adenosine receptors. However, at the present time we cannot exclude the possibility that the inhibitory effect of cyclosporin A on 2-chloroadenosine- induced apoptosis may be mediated through a calcineurin-independent process.