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

Purpose: The enhancing effect of natural interferon-beta (n-IFN-beta) or re combinant interferon-beta (r-IFN-beta) on radiation damage in tumor cells h as been evaluated in several sudies. It is not clear whether the different forms of IFN-beta available today are equally efficient in modulating the i ntrinsic radiosensitivity of tumor cells. The purpose of this study was to compare the radiosensitizing effect of n-IFN-beta, r-IFN-beta 1a, and r-IFN -beta 1b in one cancer cell line. Methods: The A549 lung-cancer cell line w as grown as a monolayer culture and incubated for 24 h with n-IFN-beta (Fib laferon), r-IFN-beta 1a (Betaserin), or r-IFN-beta 1b (Betaferon). Thereaft er. the cultures were irradiated with single graded doses of 0, 1, 2, 4, an d 6 Gy. Cellular survival was counted in a colony-forming assay at 10 days after treatment. Survival curves were established using the linear quadrati c model. Statistical comparison of the survival data was performed using St udent'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 s hown in the alteration of the survival curves and the isobologram analysis. The isoeffective concentration of r-IFN-beta 1b was 2.7-fold higher than t hat of r-IFN-beta 1a or n-IFN-beta. All three interferons increased the alp ha-component of the survival curves in a concentration-dependent way, sugge sting an influence on repair of radiation damage. The maximal sensitizing e nhancement ratio (SER) obtained with n-IFN-beta or r-IFN-beta 1a at 3000 IU /ml was 1.66 and 1.51, respectively. The highest SER, obtained with r-IFN-b eta 1b, at 8000 IU/ml was 1.93. Conclusions: All three interferons tested c an equally modify the intrinsic radiosensitivity of A549 cells. The isoeffe ctive concentration of r-IFN-beta 1b is 2.7-fold that of n-IFN-beta or r-IF N-beta 1a.