Bystander effect caused by cytosine deaminase gene and 5-fluorocytosine in vitro is substantially mediated by generated 5-fluorouracil
Kuriyama, S.; Masui, K.; Sakamoto, T.; Nakatani, T.; Kikukawa, M.; Tsujinoue, H.; Mitoro, A.; Yamazaki, M.; Yoshiji, H.; Fukui, H.; Ikenaka, K.; Mullen, C.A.; Tsujii, T.
Anticancer Research 18(5a): 3399-3406
1998
ISSN/ISBN: 0250-7005 PMID: 9858915 Document Number: 496616
Because it appears impossible to transfer toxic genes to all the cells of a cancer, the bystander effect is critical to induce effective antitumor effects. In the present study, possible in vitro mechanisms of the bystander effect by the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) were investigated. CDtransduced cancer cells exhibited much higher sensitivity to 5-FC compared to parental cells. CD-transduced cells caused killing of neighboring parental cells in the presence of 5-FC, irrespective of direct cell- to-cell contact. Media conditioned by CD-transduced cells and 5-FC contained considerable amounts of 5-fluorouracil (5-FU) and exhibited profound cytotoxicity on parental cells. Furthermore, this killing ability of conditioned media correlated well with 5-FU levels converted from 5-FC by CD-transduced cells. CD was shown not to be secreted into media from cells. These results indicate that diffusible 5-FU plays the substantially causative role in the in vitro bystander effect caused by the CD/5-FC system.