GAP-JUNCTIONS PLAY A ROLE IN THE BYSTANDER EFFECT OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GANCICLOVIR SYSTEM IN-VITRO

Tumor cells transduced with the herpes simplex virus thymidine kinase (HSVtk) gene are sensitive to the anti-viral drug ganciclovir (GCV). H owever, nearby untransduced tumor cells are also efficiently killed. T he mechanism of this 'bystander effect' was studied by comparing pairs of tumor cell lines transfected with connexin genes that differed onl y in their degree of gap junctional communication. More efficient cell killing was uniformly seen in connexin transfectants compared with th e less coupled cell lines. These results provide direct evidence that gap junctional communication plays an important role in mediating the bystander effect of the HSVtk/GCV system in vitro and have important p rognostic and therapeutic implications for future gene therapy trials.