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Investigation into the effects of cidofovir on an in vitro model of recurrent respiratory papillomatosis
Author(s) -
Donne A.J.,
Hampson L.,
He X.,
Rothera M.P.,
Homer J.J.,
Hampson I.N.
Publication year - 2006
Publication title -
clinical otolaryngology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.914
H-Index - 68
eISSN - 1749-4486
pISSN - 1749-4478
DOI - 10.1111/j.1749-4486.2006.01236_2.x
Subject(s) - cidofovir , recurrent respiratory papillomatosis , cell culture , medicine , cell cycle , papilloma , cell , cancer research , virology , in vitro , virus , pharmacology , biology , pathology , cancer , genetics
Problem. Recurrent respiratory papillomatosis (RRP) has no cure, and cidofovir is currently the most contemporary adjuvant treatment. Cidofovir has reported activity against Human Papilloma Virus type 16, but no laboratory studies have yet been performed on HPV type 6 which is the main cause of RRP. This work describes the generation of a novel HPV 6 related cell line and its use to evaluate the effects of Cidofovir. Method. HPV6b E6 cDNA was stably introduced into HPV negative C33A cervical carcinoma cells to produce the C33AT6E6 cell line. Two different doses of Cidofovir were applied to parent C33A, C33AT6E6 and C33AT16E6 (type 16 cell line) with appropriate controls. Growth and FACS cell cycle analysis were performed after 3 and 6 days of continuous exposure followed by 2 and 3 days post‐drug withdrawal. Result. PCR analysis confirmed HPV6 E6 expression in C33AT6E6 cells. High dose cidofovir was toxic at 3 and 6 days exposure in all cells tested. Low dose exposure was toxic for C33AT16E6 cells at 3 days whereas C33A and C33AT6E6 only showed minimal toxicity at 6 days. C33A and C33AT6E6 cells also showed earlier recovery following drug withdrawal. Conclusion. Cidofovir showed varying degrees of non‐specific toxicity against all three cell lines tested. However, HPV16 E6 expressing cells were more sensitive than either parent or HPV6 E6 expressing cells indicating that cidofovir has no selective advantage for the RRP related HPV6 E6 expressing cell line.