Recombinant AAV9-TLK1B Administration Ameliorates Fractionated Radiation-Induced Xerostomia

• DOI: 10.1089/hum.2012.235
• Publication Date: 2013-04-24T15:53:40Z
• Authors: Prakash Srinivasa...; Robert D. Dayton; Senthilnathan Pal...; Fleurette Abreo; Gloria Caldito; Ronald L. Klein; Gulshan Sunavala-...
• Keywords: Male; Recombination, Genetic; 0301 basic medicine; 0303 health sciences; Genetic Vectors; Submandibular Gland; Acinar Cells; Dependovirus; Protein Serine-Threonine Kinases; Xerostomia; Cell Line; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; HEK293 Cells; Transduction, Genetic; Animals; Humans; Dose Fractionation, Radiation; Transgenes; Radiation Injuries; Salivation

Salivary glands are highly susceptible to radiation, and patients with head neck cancer treated radiotherapy invariably suffer from its distressing side effect, salivary hypofunction. The reduction in saliva disrupts oral functions, significantly impairs health. Previously, we demonstrated that adenoviral-mediated expression of Tousled-like kinase 1B (TLK1B) rat submandibular preserves function after single-dose ionizing radiation. To achieve long-term transgene for protection gland against fractionated this study examines the usefulness recombinant adeno-associated viral vector TLK1B delivery. Lactated Ringers or AAV2/9 either GFP cassette were retroductally delivered (10(11) vg/gland), animals exposed, not, 20 Gy eight fractions 2.5 Gy/day. transduced predominantly ductal cells, including convoluted granular tubules glands. Transgene virus delivery could be detected within 5 weeks, stable gene was observed till end study. Pilocarpine-stimulated output measured at 8 weeks completion radiation >10-fold flow saline- AAV2/9-GFP-treated compared respective nonirradiated groups (90.8% 92.5% flow, respectively). Importantly, there no decrease stimulated irradiation pretreated AAV2/9-TLK1B (121.5% increase flow; p<0.01). histology better preserved TLK1B-treated group, though not significantly, control groups. Single preemptive averts dysfunction resulting Although transduces mostly cells gland, their assists preserving function. treatment prove beneficial attenuating xerostomia undergoing radiotherapy.