Intercellular communication, three-dimensional cell contact and radiosensitivity.

When electrically coupled mammalian cells are cultured as spherical clones (spheroids) and exposed to ionizing radiation they are less radiosensitive than monolayers of the same cell line. Investigations into the possible role of coupling (gap junctions) and three-dimensional contact in the expression of this phenomenon revealed 1) a correlation between cell coupling and the activity of adenylate cyclase in monolayers, 2) a sharp drop of cyclase activity in spheroids of coupled cells compared to monolayers, and 3) a decrease of coupling with age ("maturation") of the spheroids. These results suggest profound physiological alterations in communicating cells induced under conditions of tight three-dimensional contact as a possible cause for the reduced radiosensitivity of spheroids.