Sensitizing human cervical cancer cells In vitro to ionizing radiation with interferon beta or gamma.
Human cervical cancer is often associated with human papilloma virus (HPV). HPV products, such as the oncoproteins E6 and E7, are known to disrupt the function of TP53 (formerly known as p53). The protein encoded by the TP53 gene plays a central role in managing cellular damage. Interferons are known to down-regulate E6/E7 and may therefore restore TP53 function and influence radiation sensitivity. We investigated whether IFNB or IFNG, at various concentrations (2- 300 IU/ml) and for a range of durations of exposure (from 48 h before to 8 h after irradiation), were able to modify the radiation response of HeLa, C4-1, Me-180, C33-A and SiHa cells. In parallel to the clonogenic assays, we analyzed the effect on the mRNA that encodes IFNB and E6 by Northern blotting in the same experimental conditions. A significant change in the initial slope of the dose-response curve was observed more consistently with IFNB than with IFNG. No changes in the mRNA or protein level of TP53 and E6 could be detected. Thus other mechanisms of action need to be investigated to explain radiosensitization with recombinant IFNB in cells of human cervical cancer cell lines.
Grüninger
L
L
Laboratory of Radiobiology, Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
Cottin
E
E
Li
Y X
YX
Noël
A
A
Ozsahin
M
M
Coucke
P A
PA
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; D016159:Tumor Suppressor Protein p53; D016899:Interferon-beta; D007371:Interferon-gamma