Distribution and toxicity resulting from adenoviral vector administration to a single salivary gland in adult rats.
Distribution and toxicity resulting from adenoviral vector administration to a single salivary gland in adult rats.
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腺病毒载体对成年大鼠单个唾液腺的分布和毒性。
DOI：
10.1034/j.1600-0714.2003.t01-1-00004.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Baum,BruceJ
中科院分区：
文献类型：
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作者：
O'Connell,BrianC;Zheng,Changyu;Jacobson-Kram,David;Baum,BruceJ
背景：我们研究了编码人组蛋白3的重组腺病毒载体AdCMVH3单次唾液腺给药的分布和毒性。方法：成年大鼠经右颌下腺注射不同剂量AdCMVH3(0、106、3 × 107、109pfu; 50µl)，随访15 d。监测食物消耗、体重增加、临床表现和血清化学，并进行尸检。通过聚合酶链反应检测载体分布，并对选定的唾液样本进行复制能力腺病毒（RCA）检测。结果：所有动物均存活至祭祀（第2、8、15天），临床表现正常。在食物摄入量、体重增加和血清化学方面没有差异。唯一一致的尸检结果是高剂量动物的目标颌下腺淋巴浸润和坏死。AdCMVH3的检测呈病毒剂量依赖性，随着时间的推移而降低，低剂量时在靶腺中优先观察到。未检测到RCA。结论：涎腺给予109pfu AdCMVH3可引起最初的局灶性病理反应和广泛的组织分布。15天内没有相关的全身毒性，低剂量主要见于腺体。
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 × 107, and 109pfu; 50 µl) 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 109pfu 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.