TREATMENT OF THYROID-CARCINOMA CELLS WITH 4 DIFFERENT SUICIDE GENE PRODRUG COMBINATIONS IN-VITRO/

To develop a suitable suicide gene/prodrug therapy for the treatment o f thyroid carcinomas, the relative therapeutic efficacy of four differ ent suicide gene/prodrug combinations was compared in thyroid carcinom as in vitro. Herpes simplex virus thymidine kinase and ganciclovir (HS V-TK/GCV), Escherichia coli cytosine deaminase and 5-fluorocytosine (C D/5FC), E coli nitroreductase and CB1954 (NTR/CB1954), and human deoxy cytidine kinase and cytosine arabinoside (dCK/AraC) were employed. The suicide genes were transduced into two thyroid carcinoma cell lines w ith retroviral vectors in which all the suicide genes were under the c ontrol of the same promoter: When the relative efficacy of four suicid e gene/prodrugs was compared with therapeutic index and degree of byst ander effect, we found a clear dissociation between these two paramete rs. Thus, HSV-TKIGCVdemonstrated the widest therapeutic index, while C D/5FC and NTR/CB1954 showed the stronger bystander effect than HSV-TK/ GCV; dCK/AraC had little efficacy. Advantages and limitations of each suicide gene/prodrug combinations are discussed.