Epidermal growth factor modification of radioresistance related to cell-cell interactions

The effect of epidermal growth factor on radiosensitivity of cells in spheroids and its relationship to radioresistance associated with cell-cell interactions was examined. A human squamous carcinoma cell lines, CaSki, was used. Epidermal growth factor present for 48 hr before irradiation reduced the plating efficiency but did not affect the radiosensitivity of cells. However, epidermal growth factor present after irradiation, that is, during the period of colony formation, reduced the plating efficiency and increased the radiosensitivity of cells from spheroids. Both effects were maximum at 10 ng/ml epidermal growth factor. The enhancement in radiation response was not related to epidermal growth factor effects on potentially lethal and sublethal damage repair. In the absence of cell-cell interactions, such as monolayer cultures and spheroids disaggregated for 15 hr before irradiation, radiosensitivity enhancement by epidermal growth factor was associated with reduced shoulder of the cell survival curve. However, in the presence of cell-cell interactions, such as intact spheroids and spheroids disaggregated immediately before irradiation, in addition to reduced shoulder, epidermal growth factor treatment increased the slope compared to that of the monolayer cultures. The results indicate that epidermal growth factor enhances cellular radiosensitivity and modifies effects of cell-cell interactions.