Abstract: Objective To evaluate the feasibility and efficacy of cytocine deaminase-thymidine kinase(CD-TK)fusion double suicide gene therapy using adenovirus mediated CD-TK gene and green fluoreseent rotein(GFP)gene combined with ganciclovir(GCV)or 5-flourocytosine(5-FC)in a murine subcutaneous bladder carcinoma model.Methods A replication defective adenovirus vector containing CD-TK gene was used.Subcutaneous tumors were established in syngenic C57BL/6 female mice with 1×106 Mb49 cells.Intratumoral injection of AdCD-TK(1.58×108 PFU,qd×days)in combination with GCV(40 mg·kg-1·d-1,ip,qd×10 days)or 5-FC(400 mg·kg-1·d-1,ip,qd×10 days)was administered in vivo for the determination of treatment efficacy in separate controlled experiments.Results In vivo experiments demonstrated that the mean volume of tumor in the group of AdCD-TK/GCV(326.58±109.56 mm3),AdCD-TK/5-FC(235.33±62.94 mm3)and AdCD-TK/(GCV+5-FC)(23.58±6.78 mm3)was reduced significantly compared with that of control group(993.51±158.32 mm3)(P=0.00),the mean volume of tumor in the group of AdCD-TK/(GCV+5-FC)was significantly less than that in the group of AdCD-TK/GCV or AdCD-TK/5-FC(P=0.04).Tumor necrosis was revealed by histomorphology compared with control animals.Conclusions Adenovirus mediated CD-TK double suicide gene combining with GCV or 5-FC could provide an effective therapy in an experimental murine bladder carcinoma by significantly inhibiting tumor growth.The treatment efficacy of AdCD-TK combining GCV and 5-FC was superior to that of AdCD-TK combining GCV or AdCD-TK combining 5-FC.