Abstract

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.

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