The combined effect of interferon beta and radiation on five human tumor cell lines and embryonal lung fibroblasts

Purpose: The combined effect of natural Interferon-beta (n-IFN-beta) and io nizing radiation was tested in vitro on 5 different tumor cell lines and 1 embryonal lung fibroblast cell line. Materials and Methods: The following cell lines were used: A549 (lung cance r), MCF-7 (breast cancer), CaSki (cervical cancer), WiDr (colon cancer), ZM K-1 (head and neck cancer), and MRC-5 (embryonal lung fibroblast line). Cel ls were incubated with n-IFN-beta (30 I.U./ml to 3000 I.U./ml) 24 h before irradiation. Irradiation was given as single dose between 1 and 6 Gy. Cell survival was evaluated using a standard colony-forming assay. Results: Incubation with n-IFN-beta enhanced the effect of radiation in all tumor cell lines tested. The maximum sensitizing enhancement ratios (SER) at the 37% survival level were: 1.66 for A549 cells, 1.47 for CaSki cells, 1.56 for MCF-7 cells, 1.40 for WiDr cells, and 1.57 for ZMK-1 cells. In the nonneoplastic MRC-5 cell line, no radiosensitizing effect of n-IFN-beta co uld be demonstrated. The linear quadratic fit of the survival curves showed an increase of the alpha-component for all tumor cell lines treated with n -IFN-beta. Conclusions: IFN-beta enhanced the effect of radiation in the tumor cell li nes, but not in the nonmalignant lung fibroblasts. The increase of the alph a component in the survival curves indicates that impaired radiation repair or the accumulation of sublethal damage might play a role for the radiosen sitizing effect of n-IFN-beta. (C) 1999 Elsevier Science Inc.