Regression of experimental liver tumor after distant intra-hepatic injection of cytosine deaminase-expressing tumor cells and 5-fluorocytosine treatment

Cytosine deaminase (CD) gene of E. coli converts the non-toxic compound 5-f luorocytosine (5-FC) into 5 fluorouracil. We have introduced a vector expre ssing the CD gene in a rat colon carcinoma cell line. Expression of the CD gene confers 5-FC sensitivity to these cells in vitro and in vivo. In a bif ocal model consisting in a simultaneous engrafment of a CD+ tumor on one lo be of the liver and a wild-type parental tumor on the opposite lobe, treatm ent with 5-FC results in regression of both type of tumors, indicating the existence of a distant bystander effect.