TRANSDUCTION OF NORMAL AND MALIGNANT ORAL EPITHELIUM BY PARTICLE BOMBARDMENT

Although genetic approaches to the treatment and prevention of oral ca ncer are being developed, there are no suitable methods of transductio n of the oral mucosa or early cancers. We therefore tested the techniq ue of particle bombardment for its ability to transduce oral cancer ce lls in vitro and normal epithelium of the hamster cheek pouch in vivo. A gene gun was used to transfer a plasmid that encoded a marker/suici de fusion gene, beta-galactosidase-thymidine kinase (GAL-TEK), under c ontrol of a CMV promoter. For comparison we used the method of lipofec tion and an adenovirus vector. Particle bombardment transduced up to 1 3% of cells in culture, resulting in a 24.3% reduction in growth in th e presence of ganciclovir. The efficiency of transduction was similar to that of lipofection but was much less than that of the adenovirus v ector, which transduced 54% of cells and completely inhibited their gr owth in the presence of ganciclovir. Transduction of the hamster cheek pouch by particle bombardment produced expression of beta-galactosida se as judged by macroscopic staining, for up to 5 days. However, histo logical examination showed that the transduced cells were rare and sup erficial, and that administration of systemic ganciclovir did not lead to any changes in the tissue. Improvements in efficiency are necessar y before the gene gun can be used in the management of oral cancer.