In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines.
BACKGROUND
This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated.


METHODS
Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents.


RESULTS
The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments.


CONCLUSIONS
Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.
Angioli
R
R
II Istituto Clinica Osterica e Ginecologica Università La Sapienza, Roma, Italy.
Sevin
B U
BU
Perras
J P
JP
Untch
M
M
Koechli
O R
OR
Nguyen
H N
HN
Steren
A
A
Schwade
J G
JG
Villani
C
C
Averette
H E
HE
D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000628:therapy; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D011829:Radiation Dosage; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy* / Q000628:therapy
D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta