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We investigated the distribution, stability and radiotoxicity of 125I-oligodeoxyribonucleotides (125I-ODN) in human fibrosarcoma HT-1080 cells to study the radiotoxic effects of the Auger electron emitter 125I delivered to the cells by ODN. METHODS We delivered 125I-ODN into the cells via complexing with a liposomal delivery system. To assess the intracellular distribution and stability of 125I-ODN delivered by the liposomal delivery system, we used autoradiography, fluorescent and confocal microscopy and electrophoresis. To study the radiotoxicity of the unbound 125I-ODN, we used a clonogenic assay. The radiotoxicity of 125I-ODN delivered by the liposomal delivery system was compared with that of freely diffusible 125I-antipyrine, membrane-excluded 125I-bovine serum albumin and DNA incorporated 125I-deoxyuridine (125I-UdR). RESULTS Oligodeoxyribonucleotides accumulated in the cell nucleus within a few hours of incubation. On the basis of the number of decays at 37% survival, 125I-ODN are 2 times more radiotoxic than 125I-antipyrine, which is freely diffusible into cells, and 8 times more radiotoxic than 125I-bovine serum albumin, which remains outside cells. However, the radiotoxicity of unbound 125I-ODN is almost 3 orders of magnitude lower than that of DNA-incorporated 125I-UdR. The 125I-ODN are not significantly degraded by intracellular nucleases during the time of uptake incubation. CONCLUSIONS The dramatic difference in radiotoxicity between 125I-ODN and 125I-UdR confirms that, despite the nuclear localization, 125I-ODN are not bound to or incorporated within the genomic DNA. Our data demonstrate that the radiotoxicity of Auger electron emitters is determined by the radiation dose delivered to nuclear DNA, not necessarily to the nucleus. Therefore, relatively high intracellular concentrations of unbound 125I-ODN can be achieved without causing significant cell death.
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
February 1971,
Biochimica et biophysica acta,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
July 1971,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
December 1992,
Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
May 1989,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
January 1981,
Biochimica et biophysica acta,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
December 1975,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
October 1994,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
August 1987,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
August 1976,
Radiation research,
O A Sedelnikova, and
I G Panyutin, and
A R Thierry, and
R D Neumann
June 2003,
Cancer biotherapy & radiopharmaceuticals,
