Molecular Consequences of the Auger Effect: The Fate of Iododeoxyuridine Following Iodine-125 Decay

Two hypotheses have been advanced to explain the extreme biological toxicity of DNA-associated¹²⁵ I: (a) high local concentrations of radiation energy from low-energy Auger electrons; (b) charge-induced molecular fragmentation in the DNA. To distinguish between these two hypotheses, an attempt was made to evaluate the molecular events associated with the Auger effect. Doubly labeled iododeoxyuridine was synthesized, with¹²⁵ I in number 5 position and¹⁴ C in number 2 position of the pyrimidine ring. To achieve the high degree of radiochemical purity required for this experiment, the doubly labeled iododeoxyuridine was subjected to three consecutive column separations using Biogel P-2 (minus 400 mesh). The final, pure sample of <tex-math>${}^{14}{\rm C}-{}^{125}{\rm I}\text{-iododeoxyuridine}$</tex-math> was incubated at 4°C for 76 days and then subjected to further column analysis. The fate of iododeoxyuridine after¹²⁵ I decay was ascertained by monitoring the distribution of¹⁴ C activity in the elution profile. The results of this experiment indicated that the decay of¹²⁵ I did not cause molecular fragmentation of iododeoxyuridine. The only effect observed was deiodination, which occurred with virtually 100% efficiency. Therefore, the hypothesis which suggests that charge-induced molecular fragmentation of the DNA may be responsible for the toxic effects of¹²⁵ I appears no longer feasible.