Differential Ganciclovir-Mediated Cytotoxicity and Bystander Killing in Human Colon Carcinoma Cell Lines Expressing Herpes Simplex Virus Thymidine Kinase

Abstract

Overview summary The transfer of HSV-TK into tumor cells and the subsequent sensitization to GCV have resulted in successful antitumor effects both in vitro and in vivo for a variety of cancers. This study focuses on evaluating and comparing two colon carcinoma cell lines for their ability to metabolize GCV and transfer phosphorylated metabolites to neighboring non-HSV-TK-expressing cells (bystander effect). Here we demonstrate differences in HSV-TK expression, GCV triphosphate accumulation, and incorporation into DNA and their effect on cytotoxicity. We also provide evidence of the transfer of phosphorylated GCV to bystander cells in a cell line deficient in gap junctional intercellular communication.