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