부산대학교 도서관

Objective: We examined the toxicity and biodistribution associated with a single administration of a first-generation, serotype 5, adenoviral vector encoding human growth hormone (hGH; AdCMVhGH) to a single rat submandibular gland in the presence of hydroxychloroquine (HCQ). Previously, we showed that hGH is primarily secreted into saliva (approximately ninefold serum level) when expressed as a transgene in salivary glands (e.g. Baum et al, 1999 ), but administration of HCQ substantially increases the hGH levels secreted into the bloodstream ( Hoque et al, 2001 ). A potential application of this observation is for patients with adult hGH deficiency. Methods: Six groups of male and female adult rats ( n = 12 each) were studied, with zero to 1.5 × 1011 particles of AdCMVhGH, ±HCQ, administered retroductally. Multiple clinical and pathological parameters, as well as vector tissue distribution, were assessed. Results: All animals survived until the scheduled day of sacrifice, and essentially no untoward events were observed clinically or at gross necropsy. We observed no vector-related effects on clinical hematology evaluations and a single, transient significant change on clinical chemistry evaluations (increased serum globulin levels). Three days after AdCMVhGH administration, the vector distributed to all tissues analyzed with the exception of gonads and heart. By day 29, most organs, other than the targeted and contralateral submandibular glands, were negative for the presence of vector. On day 3, none of the animals tested positive for the presence of replication competent adenovirus in either their blood or saliva. Conclusion: Salivary gland delivery of AdCMVhGH ±HCQ appears associated with limited toxicity in rats. [ABSTRACT FROM AUTHOR]