Sensitization of renal carcinoma to radiation using alpha interferon (IFNA) gene transfection.
The rationale for this study was that local delivery of interferon-alpha (IFN-alpha) by gene transfection may be of value during radiotherapy. To investigate the feasibility of this approach, cells of the human renal carcinoma cell line R11 were transfected with the IFNA gene and evaluated for radiation responses in vitro by clonogenic assays. R11 cells expressing IFN-alpha after gene transfection were more sensitive to radiation than R11 control cells (SF2 = 0.33 and 0.51, respectively). In addition to increasing radiosensitivity, IFNA gene transfection slowed cellular growth and reduced the plating efficiency in clonogenic assays. The addition of exogenous rhIFN-alpha to cells at different times relative to irradiation showed that its presence during the postirradiation period was critical for radiosensitization, but repair of sublethal damage did not seem to be affected. No apoptosis of R11 cells was found 1-5 days after exposure to 2-25 Gy with or without IFN-alpha. Extensive formation of multinuclear giant cells was present beginning 2 days after irradiation; however, IFN-alpha did not cause any major alterations in the yield of radiation-induced giant cells. These studies suggest that gene transfection might be an effective means of delivering IFN-alpha for clinical use in radiotherapy of cancer.
Syljuåsen
R G
RG
Department of Radiation Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095, USA.
Belldegrun
A
A
Tso
C L
CL
Withers
H R
HR
McBride
W H
WH
D002292:Carcinoma, Renal Cell / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000235:genetics; D007680:Kidney Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D011838:Radiation-Sensitizing Agents