title: Induction of a bystander effect in HeLa cells by using a bigenic vector carrying viral thymidine kinase and connexin32 genes.
abstract: We previously showed that gap junction intercellular communication mediates the bystander effect in anticancer gene therapy with the herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir. Because most cancer cell lines have lost their ability to communicate through gap junctions, we investigated whether we could induce such a communication by transferring a gene for a gap junction. We transfected a vector carrying the HSV-tk (tk) and gap junction (connexin (Cx) 32) genes (Cx32(+)tk(+)) into noncommunicating HeLa cells. We compared the cytotoxicity of ganciclovir with mixtures of these cells and HeLa cells that expressed (Cx32(+)) or did not express (Cx32(-)) the Cx32 gene. The bystander effect was strong when the two mixed cell types expressed Cx32 (i.e., Cx32(+)tk(+) cells and Cx32(+)tk(-) cells). Only 25% of cells survived in this communicating mixture, even when only 10% of the cells were Cx32(+)tk(+). There was also a moderate bystander effect when the Cx32(+)tk(+) cells were mixed with noncommunicating HeLa cells in a 50% ratio. These results demonstrated that the bystander effect is enhanced by Cx32 and suggested that expression of Cx in only one cell type in a mixture can cause a bystander effect. Mol. Carcinog. 30:176--180, 2001.
authors: Multistage Carcinogenesis Unit, International Agency for Research on Cancer, Lyon, France.
authors: T
authors: T
authors: Tanaka
authors: H
authors: H
authors: Yamasaki
authors: M
authors: M
authors: Mesnil
mesh_terms: D001761:Bleomycin / Q000494:pharmacology; D017630:Connexins / Q000235:genetics*; D004351:Drug Resistance; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D000097002:Gap Junction beta-1 Protein
chemical_list: D001761:Bleomycin; D017630:Connexins; D005819:Genetic Markers; D013937:Thymidine Kinase; D000097002:Gap Junction beta-1 Protein; C105427:Zeocin