Cytotoxicity of 125I decay produced lesions in chromatin

In the authors' model of DNA damage produced by 125I, the M-XY Auger electron energy range corresponds with the diameter of a solenoid fiber in chromatin structure. Cell survival studies confirm the cytotoxicity of 125I decay especially when 125I is randomly incorporated into the nuclear genome (D0=96 decays/cell) and not in other subcellular organelles (e.g. mitochondrial DNA). Within the nucleus, cytotoxicity is increased three fold when only 5% of the nuclear genome is labelled with 125I (D0=30 decays/cell). Incorporation of 125I into only 5% of the genome was achieved by labelling cells in the presence of aphidicolin. The mechanism of the increased radiosensitivity is not due to a predisposed state in the cells to altered DNA damage or repair as measured by alkaline filter elution nor to selective irradiation of replication forks. (author)