The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status.

Abstract Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP 53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP 53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP 53 -/- cells. Moreover, the TP 53 -/- cells showed a significantly elevated frequency of apoptosis, while TP 53 +/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at lower doses whereas wild type cells only at higher doses. Secretion of IL-8 by TP 53−/− control cells was many times lower than that by TP 53 +/+ but increased significantly after irradiation. Transcription of the NFκBIA was induced in irradiated TP 53+/+ mainly, but in bystanders a higher level was observed in TP 53−/− cells, suggesting that TP 53 is required for induction of NFκB pathway after irradiation but another mechanism of activation must operate in bystander cells.