Cidofovir induces an increase in levels of low-risk and high-risk HPV E6.
BACKGROUND
Cidofovir is a nucleoside analogue that is used off-license to treat recurrent respiratory papillomatosis (RRP) caused by HPV6/11. However, the effect of this drug upon low-risk HPV 6/11 gene expression is unknown.


METHODS
The expression of E6 was evaluated by RT-PCR in HPV-ve C33A cervical carcinoma cells stably transfected with both low- and high-risk HPV E6 cDNA's and in SiHa (HPV16+ve) cervical carcinoma cells after treatment with 2 doses and durations of exposure to cidofovir.


RESULTS
Compared to the vector only transcript, E6 RNA levels showed an 8-fold increase in low-risk and 20-fold increase in high-risk E6-expressing cells. High-risk E6 protein levels were also detected by Western blot in cidofovir-treated C33A Type16 E6-transfected cells.


CONCLUSIONS
These data may indicate a potential rationale for increased risk of genetic instability and thus transformation due to drug-induced increase in the level of E6.
Donne
Adam J
AJ
University of Manchester Gynaecological Oncology Laboratories, St. Mary's Hospital, Hathersage Road, Manchester M13 OJH, United Kingdom.
Hampson
Lynne
L
He
Xiaotong T
XT
Rothera
Michael P
MP
Homer
Jarrod J
JJ
Hampson
Ian N
IN
D000998:Antiviral Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D052163:Human papillomavirus 6 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000187:drug effects* / Q000378:metabolism*; D063065:Organophosphonates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012367:RNA, Viral / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
D000998:Antiviral Agents; C118860:E6 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D063065:Organophosphonates; D012333:RNA, Messenger; D012367:RNA, Viral; D003596:Cytosine; D000077404:Cidofovir