Effects of cidofovir on a novel cell-based test system for recurrent respiratory papillomatosis.
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.
Donne
Adam J
AJ
University of Manchester Gynaecological Oncology Laboratories, St Mary's Hospital, Hathersage Road, Manchester M13 OJH, United Kingdom. ajdonne@doctors.org.uk
Hampson
Lynne
L
He
Xiao T
XT
Rothera
Michael P
MP
Homer
Jarrod J
JJ
Hampson
Ian N
IN
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015153:Blotting, Western; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000187:drug effects; D052163:Human papillomavirus 6 / Q000187:drug effects*; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D010039:Otorhinolaryngologic Neoplasms / Q000188:drug therapy* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir