Bystander effect from cytosine deaminase and uracil phosphoribosyl transferase genes in vitro: a partial contribution of gap junctions.

Toshiaki Tanaka (1) , Agnès Duflot-Dancer (1) , Michèle Tiraby (2) , Colette Piccoli (1) , Gérard Tiraby (2, 3) , Hiroshi Yamasaki (1) , Marc Mesnil (4)

1 Unit of Multistage Carcinogenesis
2 InvivoGen
3 Laboratoire de Microbiologie et Génétique Appliquées
4 IPBC - Institut de physiologie et biologie cellulaires

Among gene therapy strategies elaborated to kill cancer cells, one uses the CodA gene, coding for cytosine deaminase (CD) that converts 5-fluorocytosine (5-FC) into toxic 5-fluorouracil (5-FU). To enhance 5-FC metabolic activation, we prepared a vector carrying CodA and upp (uracil phosphoribosyl transferase) genes which rendered HeLa cells sensitive to 5-FC and enhanced a bystander effect not mediated by gap junctions. However, 1% CD(+)-UPP(+) cells were able to kill 40% of the cell population if the cells were communicating. This suggests that, at very low percentages of CD(+)-UPP(+) cells, CodA and upp induce a bystander effect through gap junction-dependent mechanisms.

Mots clés: Bystander effect; Gap junction; Cytosine deaminase; Uracil phosphoribosyl transferase; Gene therapy

Domaines: Biologie moléculaire; Interactions cellulaires [q-bio.CB]; Cancer

Toshiaki Tanaka, Agnès Duflot-Dancer, Michèle Tiraby, Colette Piccoli, Gérard Tiraby, et al.. Bystander effect from cytosine deaminase and uracil phosphoribosyl transferase genes in vitro: a partial contribution of gap junctions.. Cancer Letters, 2009, 282 (1), pp.43-47. ⟨10.1016/j.canlet.2009.02.050⟩. ⟨hal-00444675⟩