The Paradoxical Nature of DNA Damage and Cell Death Induced by¹²⁵ I Decay

Chinese hamster ovary cells were synchronized at the G₁/ S-phase boundary of the cell cycle and pulse-labeled for 10 min with${}^{125}{\rm I}\text{-iododeoxyuridine}$ 30 min after entering the S phase. Cell samples were harvested for freezing and${}^{125}{\rm I}\text{-decay}$ accumulation at intervals ranging from 15 to 480 min after termination of labeling. The survival data showed a marked shift from cell killing characteristic of low-LET radiation to that more characteristic of killing by high-LET radiation with increasing intervals between DNA pulse-labeling and decay accumulation. Cells harvested and frozen within 1 h after pulse-labeling yielded a low-LET radiation survival response with a pronounced shoulder and a large D₀ of up to 0.9 Gy. With longer chase periods the shoulder and the D₀ decreased progressively, and cells harvested 5 h after pulse-labeling or later exhibited a high-LET survival response (D₀: 0.13 Gy). Two interpretations for these findings are discussed. (1) If DNA is the sole target for radiation death, the results indicate that DNA maturation increases radiation damage to DNA or reduces damage repair. (2) If radiation cell death involves damage to higher-order structures in the cell nucleus, the findings suggest that newly replicated DNA is not attached to these structures during the initial low-LET period, but¹²⁵ I starts to induce high-LET radiation effects as labeled DNA segments become associated with the target structure(s). On balance, our data favor the latter interpretation.