cAMP stimulates the bystander effect in suicide gene therapy of human choriocarcinoma

In gene therapy, tumor cells expressing herpes simplex virus thymidine kina se (HSV-tk) are sensitive to ganciclovir (GCV) and HSV-tk positive cells ex posed to GCV are lethal to adjacent HSV-tk negative cells. This phenomenon has been called the bystander effect, and the gap junction is thought to me diate it. In this study, sensitivity to GCV and bystander effect in a human choriocarcinoma cell line, BeWo, transfected with HSV-tk were investigated . Furthermore, the effect of 8-bromo-cAMP on bystander effect and connexin4 0 gene transcription were examined. HSV-tk positive cells were sensitive to GCV at the concentration of 10 mu g/ml in a time-dependent manner. The gro wth of HSV-tk negative cells was inhibited when the population of cultured cells contained more than 10% HSV-tk positive cells and 8-bromo-cAMP enhanc ed bystander effect 8-bromo- cAMP increased connexin40 mRNA expression and gap junctional intercellular communication.