title: Bystander effect from cytosine deaminase and uracil phosphoribosyl transferase genes in vitro: a partial contribution of gap junctions.
abstract: 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.
authors.affiliation: Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon cedex 08, France.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Agnès
authors.initials: A
authors.lastname: Duflot-Dancer
authors.forename: Michèle
authors.initials: M
authors.lastname: Tiraby
authors.forename: Colette
authors.initials: C
authors.lastname: Piccoli
authors.forename: Gérard
authors.initials: G
authors.lastname: Tiraby
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Marc
authors.initials: M
authors.lastname: Mesnil