W-7, a calmodulin inhibitor, potentiates dacarbazine cytotoxicity in human neoplastic cells

Dacarbazine induces damage in replicative DNA, with a maximum level at 24 hr after treatment. Repair of these lesions does not occur when cells are post-treated with the calmodulin inhibitor W-7. In parallel cell cytotoxicity increases. The augmentation effect of W-7 is prevented by simultaneous incubation of cells with high levels of calmodulin and does not occur in cells pre-treated with aphidicolin (to stop DNA synthesis). Furthermore, W-5, an analogue of W-7 with a less inhibitory effect on calmodulin, does not interfere with DNA repair. The results show that calmodulin and/or calmodulin-regulated proteins are involved in the repair process of dacarbazine-induced DNA lesions.