Department of Botany and Zoology

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Browsing Department of Botany and Zoology by browse.metadata.advisor "Bohm, J. F."

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    Cellular radiotoxicity of iodine-123
    (Stellenbosch : Stellenbosch University, 2000-03) Smit, B. S.; Bohm, J. F.; Reinecke, S. A.; Stellenbosch University. Faculty of Science. Dept. of Botany and Zoology.
    ENGLISH ABSTRACT: The Auger electron emitter iodine-123 was examined in the form of 4- [12311iodoantipyrineand as [12311Nal for its effectiveness in killing cells of different sensitivity to photon irradiation. Micronucleus assays showed that 4- [12311iodoantipyrineis two to three times more effective in cell inactivation than C2311Nai.This can be attributed to the fact that antipyrine, for reason of its lipid solubility, can enter cells and can reach the cell nucleus, whereas C231]Nai is excluded from the cytoplasm. The differential targeting of intra- and extracellular compartments was confirmed by radionuclide uptake experiments. In the nucleus, Auger decay conceivably is located on the DNA where it may invoke high-LET irradiation damage. Irradiation damage by [12311Naisl by long range y-irradiation and hence low-LET. Results of the present study demonstrate however that the enhancement of MN-frequency seen with 4-[123I]iodoantipyrine over [12311Nalis similar for all cell lines and that the narrowing of MN-response expected for 4- [12311iodoantipyrinedoes not occur. Experiments with the free radical scavenger, DMSO, indicated nearly identical dose reduction factors for both iodine-123 carriers. These two observations strongly suggest that the cell inactivation by 4- [12311iodoantipyrine is not by high-LET direct ionisation of DNA, but due to an indirect effect. The indirect radiation effect of Auger decay in the nucleus is attributed to shielding of DNA by histones. Such a protection mechanism is not unrealistic if it is realised that histones and DNA associate in a 1: 1 weight ratio and that higher order folding of the nucleosome chain into solenoids, loops, and chromatids generates considerable protein density. In the nucleosome core, the histone acta mer measures 7 nm and closely approximates the 10 nm dimention of the Auger electron range. It is suggested that the interlacing of protein density with DNA density suppresses direct ionisation from Auger decay at the DNA and directs the majority of Auger decay to the histones.