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西多福韦对一种用于复发性呼吸道乳头状瘤病的新型细胞检测系统的影响。

Effects of cidofovir on a novel cell-based test system for recurrent respiratory papillomatosis.

作者信息

Donne Adam J, Hampson Lynne, He Xiao T, Rothera Michael P, Homer Jarrod J, Hampson Ian N

机构信息

University of Manchester Gynaecological Oncology Laboratories, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, United Kingdom.

出版信息

Head Neck. 2007 Aug;29(8):741-50. doi: 10.1002/hed.20572.

Abstract

BACKGROUND

Cidofovir has been reported to have activity against human papillomavirus (HPV) type 16, but no laboratory studies have been performed on HPV type 6, the main cause of recurrent respiratory papillomatosis (RRP).

METHODS

HPV6b E6 cDNA-based C33A (non-HPV cervical carcinoma) cell line was produced. Two different doses of cidofovir were applied to parent C33A, C33AT6E6, and C33AT16E6 (HPV 16). Growth and flow cytometry analysis were performed.

RESULTS

Polymerase chain reaction confirmed HPV6 E6 expression in C33AT6E6 cells. High-dose cidofovir was found to be toxic to all cell lines. Low-dose exposure was found to be toxic to C33AT16E6 cells at 3 days, whereas C33A and C33AT6E6 showed minimal toxicity at 6 days and earlier recovery following drug withdrawal.

CONCLUSIONS

Cidofovir showed nonspecific toxicity against all 3 cell lines tested. HPV16 E6 expressing cells were more sensitive than parent or HPV6 E6 expressing cells. Cidofovir has no selective advantage for the RRP-related HPV6 E6 expressing cell line.

摘要

背景

已报道西多福韦对16型人乳头瘤病毒(HPV)具有活性,但尚未对复发性呼吸道乳头瘤病(RRP)的主要病因6型HPV进行实验室研究。

方法

构建了基于HPV6b E6 cDNA的C33A(非HPV宫颈癌)细胞系。将两种不同剂量的西多福韦应用于亲代C33A、C33AT6E6和C33AT16E6(HPV 16)细胞系。进行生长和流式细胞术分析。

结果

聚合酶链反应证实C33AT6E6细胞中存在HPV6 E6表达。发现高剂量西多福韦对所有细胞系均有毒性。低剂量暴露在3天时对C33AT16E6细胞有毒性,而C33A和C33AT6E6在6天时显示出最小毒性,停药后恢复较早。

结论

西多福韦对所有测试的3种细胞系均表现出非特异性毒性。表达HPV16 E6的细胞比亲代或表达HPV6 E6的细胞更敏感。西多福韦对RRP相关的表达HPV6 E6的细胞系没有选择性优势。

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