Radionuclide Toxicity in Cultured Mammalian Cells: Elucidation of the Primary Site for Radiation-Induced Division Delay

Chinese hamster ovary cells, arrested in late S or early G1 phase, were exposed to various doses of membrane-associated125 I (administered as125 I-labeled, monovalent concanavalin A) and DNA-associated125 I (administered as ¹²⁵ I-iododeoxyuridine . Cell division was evaluated by monitoring the formation of duplet cells in monolayer. On the basis of radionuclide incorporation data, cellular dimensions, and subcellular radionuclide distributions, the cumulative dose to various subcellular regions was calculated from the known decay properties of125 I. In terms of125 I decays/cell, plasma membrane-associated125 I was very inefficient in producing division delay (0.01 min/decay), whereas DNA-associated125 I was extremely effective (1.45 min/decay). In terms of radiation dose to the cell nucleus, membrane-associated125 I caused exactly the same division delay as external X irradiation (0.45 min/rad), but nuclear125 I remained much more toxic (1.80 min/rad). These findings...