Untersuchungen zur Beeinflussung des Wachstums eines Experimentaltumors der Maus (Sarkom 180) durch Langzeitinfusion von $^{125}$Joddesoxyuridin
Untersuchungen zur Beeinflussung des Wachstums eines Experimentaltumors der Maus (Sarkom 180) durch Langzeitinfusion von $^{125}$Joddesoxyuridin
Variously in the past tumor cells were labeled in vivo with $^{125}$I-iododeoxyuridine ($^{125}$IUdR) for studies of cell proliferation. IUdR is a thymidine analogue and thus may be incorporated in DNA during synthesis. Following $^{125}$ I-decay by electron capture low energy Auger- and conversion...
Saved in:
Personal Name(s): | Wirtz, F. (Corresponding author) |
---|---|
Contributing Institute: |
Publikationen vor 2000; PRE-2000; Retrocat |
Imprint: |
Jülich
Kernforschungsanlage Jülich, Verlag
1987
|
Physical Description: |
61 p. |
Document Type: |
Report Book |
Research Program: |
ohne Topic |
Series Title: |
Berichte der Kernforschungsanlage Jülich
2133 |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Variously in the past tumor cells were labeled in vivo with $^{125}$I-iododeoxyuridine ($^{125}$IUdR) for studies of cell proliferation. IUdR is a thymidine analogue and thus may be incorporated in DNA during synthesis. Following $^{125}$ I-decay by electron capture low energy Auger- and conversion electrons, about 20 on the average, are emitted and cause considerable biological damage when released close to or in DNA. Furthermore, there is reason to assume that the chemical transformation from I to Te and Coulomb repulsion of the residual positive charges of the daughter nucleus $^{125}$Te add considerably to the effects caused by the electrons, X-rays and $\gamma$-rays. The present experiments were designed to test the therapeutic qualification of $^{125}$1 incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of $^{125}$IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3 x 10$^{5}$ tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 $\mu$Ci infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. Measurements of tumor volumes with a calliper in two plains and of retained radioactivities - in a NaI(Tl)-whole body counter for small animals - served for indicators for the effectiveness of the infusions. In comparison with tumors of control animals tumors of mice infused with $^{125}$IUdR showed a mean retardationin growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1 % of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. The results of the experiments indicate beneficial therapeutic effects of $^{125}$IUdR incorporated in tumor cell DNA. It is suggested to expand the applied technique - specifically with respect to variations of the parameters of the experimental procedures - in order to further increase its effectiveness regarding the impairment of tumor growth. |