Radiosensitizing effect of natural and recombinant β-interferons in a human lung carcinoma in vitro

Purpose: The enhancing effect of natural interferon-β (n-IFN-β) or recombinant interferon-β (r-IFN-β) on radiation damage in tumor cells has been evaluated in several studies. It is not clear whether the different forms of IFN-β 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-β, r-IFN-β1a, and r-IFN-β1b 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-β (Fiblaferon), r- IFN-β1a (Betaserin), or r-IFN-β1b (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-β and radiation were evaluated using isobologram analysis. Results: All three types of IFN-β 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-β1b was 2.7-fold higher than that of r- IFN-β1a or n-IFN-β. All three interferons increased the α-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-β or r-IFN-β1a at 3000 IU/ml was 1.66 and 1.51, respectively. The highest SER, obtained with r-IFN-β1b, 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-β1b is 2.7-fold that of n-IFN-β or r-IFN-β1a.