EXTRACELLULAR-MATRIX (ECM) AND CYTOSKELETAL MODULATION OF CELLULAR RADIOSENSITIVITY

Modulation of radiosensitivity by components of the extracellular matr ix (ECM) and cytoskeletal elements has not been adequately studied. Al though differences in the radiosensitivities of cells grown as monolay ers, as spheroids, or grown in vitro in animal models are known, expla nations have in the past neglected possible influences by the ECM and cytoskeleton. Using collagen gel cultures, it is shown that the fibril lar component of the ECM (which is responsible for cell anchorage) ind uces shifts in radiosensitivity. The effect is critically dependent on the affinity of the cell type towards collagen. The shifts in radiose nsitivity induced by ECM alteration are manifested as changed D-q valu es. By applying four specific cytoskeletal poisons which either stabil ize or destabilize specific cytoskeletal elements, the involvement of microfilaments and microtubuli was qualitatively appraised. Cytochalas in B, which destabilizes microfilaments (by preventing polymerization) , caused a significant rise in radioresistance. This rise was due to i ncreased D-0. Although the cellular morphological change accompanying cytochalasin B treatment was essentially similar to that obtained with trypsin, the respective shifts in radioresponses were qualitatively d ifferent and opposite, suggesting differences in mechanism of action.