Reference : A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Vi...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/18491
A Cell Type-Specific and Gap Junction-Independent Mechanism for the Herpes Simplex Virus-1 Thymidine Kinase Gene/Ganciclovir-Mediated Bystander Effect
English
Princen, Frederic [ > > ]
Robe, Pierre mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Lechanteur, Chantal mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
Mesnil, M. [> > > >]
Rigo, Jean-Marie mailto [Université de Liège - ULg > Département Argenco : Secteur GeMMe > Matériaux non métal. & Procédés d'exécution des construct. >]
Gielen, Jacques [ > > ]
Merville, Marie-Paule mailto [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
Bours, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine]
Nov-1999
Clinical Cancer Research : An Official Journal of the American Association for Cancer Research
American Association for Cancer Research, Inc. (AACR)
5
11
3639-44
Yes (verified by ORBi)
International
1078-0432
[en] Tumor cells expressing the herpes simplex virus type 1 thymidine kinase (HSV-tk) gene are killed by nucleoside analogues such as ganciclovir (GCV). GCV affects not only the cells expressing HSV-tk but also neighboring cells that do not express the gene; this phenomenon commonly is called "bystander effect." GCV metabolites transfer via gap junctional intercellular communication (GJIC) accounts for the bystander effect in different cell lines, but other mechanisms have also been described. In this study, we analyzed the mechanisms of the bystander effect in two cell lines exhibiting different capacities of communication (DHD/K12 and 9L). The 9L cells exhibited a very good bystander effect, which was completely blocked by a long-term inhibitor of GJIC, 18 alpha-glycyrrhetinic acid. DHD/K12 cells exhibited a moderate bystander effect that was not abolished by 18 alpha-glycyrrhetinic acid or 1-octanol, another strong inhibitor of GJIC. Interestingly, we also observed a bystander effect in cultures where HSV-tk-expressing DHD/K12 cells were physically separated from their untransfected counterparts but grown in the same medium. Moreover, the transfer of filtered conditioned medium from GCV-treated HSV-tk-expressing DHD/K12 cells to DHD/K12 parental cells induced a decrease of survival in a concentration-dependent manner, suggesting that the bystander effect in this cell line was mediated by a soluble factor.
http://hdl.handle.net/2268/18491

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