The trp gene family has been proposed to encode the store-operated Ca 2؉ influx (SOC) channel(s

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat submandibular glands following IR restored salivary flow to near normal levels. It is unclear if this strategy is useful in larger animals. Herein, we evaluated AdhAQP1-mediated gene transfer after parotid gland IR (20 Gy) in the miniature pig. Sixteen weeks following IR, salivation from the targeted gland was decreased by >80%. AdhAQP1 administration resulted in a dose-dependent increase in parotid salivary flow to approximately 80% of pre-IR levels on day 3. A control Ad vector was without significant effect. The effective AdhAQP1 dose was 2.5 x 10(5) pfu/microl infusate, a dose that leads to comparable transgene expression in murine and minipig salivary glands. Three days after Ad vector administration little change was observed in clinical chemistry and hematology values. These findings demonstrate that localized delivery of AdhAQP1 to IR-damaged salivary glands increases salivary secretion, without significant general adverse events, in a large animal model.

We have previously suggested that although salivary were approximately 16 ng/ml and rat insulin-like growth glands function in an exocrine manner they might none the factor-1 was elevated approximately 25%. Moreover, less offer a useful way to deliver therapeutic proteins sysserum chemistry profiles of rats subjected to in vivo gene temically. As a direct functional test of this hypothesis, we transfer displayed alterations in the BUN:creatinine ratio constructed a recombinant adenovirus (AdCMVhGH) and triglyceride levels presumably reflecting the anabolic encoding human growth hormone (hGH) and then studied actions of the hGH. These results provide the first demonthe biological action of hGH produced following transfer of stration of systemic biological action from a transgene prothe hGH gene to rat submandibular glands. At 48 h followduct secreted in an endocrine fashion from the salivary ing infusion of AdCMVhGH into these glands via canglands. nulation of the main excretory duct, serum levels of hGH

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