Distribution and toxicity resulting from adenoviral vector administration to a single salivary gland in adult rats.
BACKGROUND
We examined the distribution and toxicity associated with a single salivary gland administration of a recombinant adenoviral vector, AdCMVH3, encoding human histatin 3.


METHODS
Adult rats received different doses of AdCMVH3 (0, 106, 3 x 107, and 109 pfu; 50 microl) via the right submandibular gland and were followed for 15 days. Food consumption, weight gain, clinical appearance, and serum chemistry were monitored, and a necropsy was performed. Vector distribution was examined by polymerase chain reaction, and selected saliva samples were tested for replication-competent adenovirus (RCA).


RESULTS
All animals survived to sacrifice (days 2, 8, and 15), and appeared normal clinically. There were no differences in food consumption, weight gain, and serum chemistry. The only consistent necropsy findings were lymphoid infiltrates and necrosis in the target submandibular glands of high-dosage animals. AdCMVH3 detection was virus dose dependent, decreased with time, and at low dose preferentially observed in the targeted gland. No RCA was detected.


CONCLUSIONS
Salivary gland administration of 109 pfu AdCMVH3 elicits an initial focal pathologic response and wide tissue distribution. There is no associated systemic toxicity up to 15 days, and lower doses are primarily found in glands.
O'Connell
Brian C
BC
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
Zheng
Changyu
C
Jacobson-Kram
David
D
Baum
Bruce J
BJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001774:Blood Chemical Analysis; D004435:Eating; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006023:Glycoproteins / Q000235:genetics*; D054808:Histatins; D006801:Humans; D008297:Male; D011506:Proteins / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D011994:Recombinant Proteins; D012463:Saliva / Q000737:chemistry; D012471:Salivary Proteins and Peptides / Q000235:genetics*; D013363:Submandibular Gland / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution; D015430:Weight Gain
D006023:Glycoproteins; C068075:HTN3 protein, human; D054808:Histatins; D011506:Proteins; D011994:Recombinant Proteins; D012471:Salivary Proteins and Peptides