There are several concerns that must be addressed when applying retroviral-mediated gene transfer to human somatic cell genetic diseases. One concern is that the vector, or components of it, may have oncogenic effects. We are investigating whether the use of retroviral vectors for gene therapy may have adverse consequences by examining the effects of such vectors on transformation or mutation of cells in vitro. The initial phase of the project involved infection of C3H10T1/2 cells with the ecotropically packaged retroviral vector backbone. The vector efficiently infects C3H10T1/2 cells and confers resistance to the antibiotic G418. Experiments performed under three different regimens demonstrated no significant decreases in survival or increases in transformation following exposure to the retrovirus vector. Subsequently, vectors containing the therapeutic human ADA cDNA driven by either the 5'-LTR or the SV40 promoter were infected into C3H10T1/2 cells; again, no increase in morphological transformation was detectable.