Recombinant E1-deleted adenoviral vectors induce apoptosis in a rat airwayepithelial mucous goblet cell line

Replication-defective adenoviruses (Ad) are used as vectors for delivering therapeutic genes to human airway cells. We examined whether El-deleted Ad vectors (AdS-CMV-LacZ) had effects on cell kinetics in SPOC1 cells, which i s a rat airway epithelial mucous goblet cell line. There was a vector multi plicity of infection (moi)-dependent increase of the transduction efficienc y of the LacZ reporter gene in SPOC cells. Cell proliferation was inhibited in the vector-infected cells compared with that in vehicle-exposed cells. However, increased cell death was observed in the vector-infected cells wit h a higher moi. The morphology of vector-exposed cells revealed apoptotic f eatures including nuclear condensation and a fragmented nucleus. These resu lts indicate that higher moi of vectors allows the cells to achieve higher gene transfer, but also induce apoptosis of infected cells. Minimizing the induction of apoptosis of vector-infected cells may be an important strateg y for the prolongation of transduction efficiency of Ad vectors in airway e pithelial mucous goblet cells.