Reduced Temperature (22°C) Results in Enhancement of Cell Killing and Neoplastic Transformation in Noncycling HeLa × Skin Fibroblast Human Hybrid Cells Irradiated with Low-Dose-Rate Gamma Radiation

The effect of reduced temperature (22°C) or serum deprivation during low-dose-rate (0.66 cGy/min) γ irradiation on cell killing and neoplastic transformation has been examined using the HeLa × skin fibroblast human hybrid cell system. The reduced temperature stops progression of these cells through the cell cycle while serum deprivation slows down cell turnover markedly. The data demonstrate an enhancement in both of the end points when cells are held at 22°C compared to parallel experiments done at 37°C. In operational terms, the decreased survival and increased neoplastic transformation are consistent with our earlier hypothesis of a higher probability of misrepair at reduced temperature (Redpath et al., Radiat. Res. 137, 323-329, 1994). The interpretation that this damage enhancement was associated with the reduced temperature, and not the fact that the cells were noncycling, was supported by the results of experiments performed with cells cultured at 37°C in serum-free medium for 35 h prior to and then during the 12.24 h low-dose-rate radiation exposure. Under these conditions, cell cycle progression, as shown by reduction in growth rate and dual-parameter flow cytometric analysis, was considerably inhibited (cell cycle time increased from 20 h to 40 h), and there was no significant enhancement of cell killing or neoplastic transformation.