Evaluation of the influence of radiation-induced cohort effect in cell populations receiving different doses

A non-targeted effect called radiation-induced cohort effect, which results in interactions among irradiated neighboring cells through cellular communication, has been reported. In high-precision radiotherapy, the dose is localized to the tumor, and rapid spatial changes occur in dose distribution. However, the effect of irradiating a population of cells with non-uniform doses remains unknown. In this study, we evaluated the influence of cohort effect by creating cell populations irradiated with different doses using human oral squamous cell carcinoma (SAS) and human lung (A549) cells.

Cell populations irradiated with different doses were created in two ways: direct contact co-culture (DCC) using a cell tracer dye and indirect contact co-culture (ICC) using cell culture inserts to assess the effects of soluble factors. Target cells were irradiated with 4 Gy and co-cultured cells with 0, 0.8, 3.2, and 4 Gy. In DCC, cell proliferation assays were performed using a flow cytometer, and in ICC, modified high-density survival, clonogenic, and apoptosis assays were performed.

In DCC, irradiation of co-cultured cells with X-rays increased the relative proliferation rate of the target cells. Similarly, irradiating co-cultured cells using ICC with X-rays increased the relative survival rate of target cells.

The results of this study showed that, even if there is a sharp decrease in dose near the tumor, the cytocidal effect on the tumor is not adversely affected. In addition, soluble factors were found to be involved in cohort effect.