Bystander effect induced by suicide gene on mouse bladder cancer

Mouse bladder cancer cell line(T839) was transfected with retroviral vcector HSVtk gene. The sensitivity of T739TK cells to GCV was detected in vitro. Bystander effect in vitro in co-cultured mixtures of T739TK and T739 cells at different ratios or at the sa,e ratio in culture bottles of different size was determined. In the mouse model of bladder tumor, mixtures of T739 and T739Tk cells were I,planted bemeath the peritonea of syngeneic mice. When tumors grew to the size of 0.5--0.8cm, intraperitoneal administration of GCV was carried out for 6d. Changes of tumor size and survical rate of mice were observed. Results T739 cells retrovirally ransfected with the HSVtk gene beca,e sensitive to low concentratiuons of GCV. Analysis by RT-PCR confirmed HSVtk expression in the transfected T739Tk cells. An absolute by stander effect was observed in the mixed culture of cells in vitro when the HSVtk gene tranfecred cells were at the retio of above 10%. The tumor growth in the animal model was significantly inhibited by GCV, demeonstrating the existence of bystander effect in vivo. The survival time of mice was prolonged after administration of GCV. Conclusion The in vitro and in vivo bystander effects exsist in mouse bladder cancer transfectred with HSVtk gene, elhancing the role HSVtk/GCV system for the treatment of bladder carcinoma.