Radiosensitizing effect of natural and recombinant beta-interferons in a human lung carcinoma in vitro.
OBJECTIVE
The enhancing effect of natural interferon-beta (n-IFN-beta) or recombinant interferon-beta (r-IFN-beta) on radiation damage in tumor cells has been evaluated in several sudies. It is not clear whether the different forms of IFN-beta available today are equally efficient in modulating the intrinsic radiosensitivity of tumor cells. The purpose of this study was to compare the radiosensitizing effect of n-IFN-beta, r-IFN-beta1a, and r-IFN-beta1b in one cancer cell line.


METHODS
The A549 lung-cancer cell line was grown as a monolayer culture and incubated for 24 h with n-IFN-beta (Fiblaferon), r-IFN-beta1a (Betaserin), or r-IFN-beta1b (Betaferon). Thereafter, the cultures were irradiated with single graded doses of 0, 1, 2, 4, and 6 Gy. Cellular survival was counted in a colony-forming assay at 10 days after treatment. Survival curves were established using the linear quadratic model. Statistical comparison of the survival data was performed using Student's t-test for each dose point. Interactions of IFN-beta and radiation were evaluated using isobologram analysis.


RESULTS
All three types of IFN-beta enhanced the radiation sensitivity of A549 cells in a similar way as shown in the alteration of the survival curves and the isobologram analysis. The isoeffective concentration of r-IFN-beta1b was 2.7-fold higher than that of r-IFN-beta1a or n-IFN-beta. All three interferons increased the alpha-component of the survival curves in a concentration-dependent way, suggesting an influence on repair of radiation damage. The maximal sensitizing enhancement ratio (SER) obtained with n-IFN-beta or r-IFN-beta1a at 3000 IU/ml was 1.66 and 1.51, respectively. The highest SER, obtained with r-IFN-beta1b, at 8000 IU/ml was 1.93.


CONCLUSIONS
All three interferons tested can equally modify the intrinsic radiosensitivity of A549 cells. The isoeffective concentration of r-IFN-beta1b is 2.7-fold that of n-IFN-beta or r-IFN-beta1a.
Schmidberger
H
H
Department of Radiation Oncology, Georg-August Universität Göttingen, Germany. hschmbg@med.uni-goettingen-de
Rave-Fränk
M
M
Lehmann
J
J
Schweinfurth
S
S
Pradier
O
O
Hess
C F
CF
D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D016899:Interferon-beta