Safety of salivary gland‐administered replication‐deficient recombinant adenovirus in rats

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Abstract
Delporte C, Miller G, Kagami H, Lillibridge CD, O'Connell BC, Atkinson JC, Baum BJ: Safety of salivary gland‐administered replication‐deficient recombinant adenovirus in rats. J Oral Pathol Med 1998; 27: 34–8. © Munksgaard, 1998.We have examined the safety of a replication‐deficient recombinant adenovirus administered at a single, high dose intraductally to rat submandibular glands or systemically via the femoral vein. The virus used directed the synthesis of human aquaporin‐1, a water channel protein, and is termed AdhAQPl. Comparisons were made 1 and 9 days post‐infection with animals administered either a similar virus encoding no transgene or the viral suspension buffer. Animals were specifically not given anti‐inflammatory drugs to impede the well‐known immunopathologic response to recombinant adenoviral administration. Serum chemistries and hematological parameters were monitored. Rats were subjected to complete gross necropsy and selected tissues were evaluated by histopathology. Most clinical chemistry and hematology values were within normal ranges; however, evidence of inflammation (e.g., elevated lactic dehydrogenase, total leukocyte count) was seen. Gross pathology was normal, as was histopathology, excepting rare focal areas of necrosis. The results show that intrasalivary gland or intravenous AdhAQPl administration leads to low levels of toxicity in rats.