Influence of interferon-gamma on radiation-induced apoptosis in normal and ataxia-telangiectasia fibroblast cell lines.

Combination of interferon-gamma (IFN-gamma) with radiation, or chemotherapeutic agents, produces different kind of modulatory effects, depending on the cell types and experimental conditions. The objective of the present study was verify the influence of IFN-gamma on the induction of apoptosis by gamma-radiation. Experiments were carried out on human fibroblast cell lines: VH-25 (primary), MRC-5, and AT-5BIVA (SV40-transformed). Exponentially growing cells were irradiated and exposed to IFN-gamma (1,000, 2,000, and 3,000 UI/mL) until in situ cell staining performed at 6, 24, and 48 h. Induction of apoptosis by ionising radiation was not verified in primary VH-25 cells. A significant increase in the frequencies of apoptotic cells was observed in SV-40-transformed cells lines, MRC-5, and AT-5BIVA fibroblasts, which were irradiated with 1.0 Gy, but the frequencies of necrotic cells were similar to the control levels. In MRC-5 cells, combined treatments with radiation and IFN-gamma induced a statistically significant reduction in the frequencies of apoptotic cells detected at 24 and 48 h after cell irradiation, while for AT cells the interaction effect (reduction of apoptosis frequency) was significant even at earlier time collection (6 h) after gamma-irradiation, and higher when compared to MRC-5 cells. The present study demonstrated that IFN-gamma showed an anti-apoptotic activity in SV40-transformed fibroblasts, normal and AT cells, which were irradiated with gamma-rays, thus indicating a mechanism dependent on the cellular type. Copyright 2001 Wiley-Liss, Inc.