Walicka, M. A., Ding, Y., Adelstein, S. J. and Kassis, A. I. Toxicity of DNA-Incorporated Iodine-125: Quantifying the Direct and Indirect Effects.

To understand the biophysical mechanism(s) underlying the induction of cell death by the decay of the Auger electron emitter iodine-125 in DNA, Chinese hamster V79 lung fibroblasts were labeled with 5-[¹²⁵I]iodo-2′-deoxyuridine (¹²⁵IdU) for two doubling times and frozen and stored at −135°C in the presence of 0.26–3.0 M dimethyl sulfoxide (DMSO), which acts simultaneously as a cryoprotector and a hydroxyl radical scavenger. After the accumulation of ¹²⁵I decays, the cells were defrosted and their survival was determined. Within the range of the number of decays examined (up to 470 disintegrations per cell), the survival curves are exponential. The dependence of the D₃₇ on DMSO concentration is triphasic and seems to reach a plateau at ∼1.3 M. By extrapolating to infinite DMSO concentration, we estimate the D₃₇ for maximal hydroxyl radical scavenging to be 411 ± 36 disintegrations per cell. To determine the D₃₇ in the absence of DMSO, we extrapolate the D₃₇ curve to zero concentration, and a D₃₇ of 54 ± 5 disintegrations per cell is obtained. The maximal dose modification factor, calculated as the ratio of the D₃₇ at infinite DMSO concentration (i.e. direct effects only) to the D₃₇ at zero DMSO concentration (i.e. direct and indirect effects), is 7.6 ± 1.0. By inference, ∼90% of the radiotoxic effects of DNA-incorporated ¹²⁵I are due to indirect mechanisms.