Some limitations of labeled compounds in radiobiological investigations of deoxyribonucleic acid (DNA) synthesis
The results of recent biophysical and biochemical investigations have demonstrated that careful experimental design is necessary to avoid erroneous or misleading results. The ratio of the speciflc activity of the labeled compound in the irradiated biological system to the labeled compound in the control is usually interpreted as a measure of the effects of irradiation on a biological process. Since specific activity of DNA is dependent upon the fraction of cells synthesizing DNA and the amount of DNA synthesized per cell per unit of time, information is needed about DNA synthesis within populations of cells. Biochemical studies alone do not provide this information. The rate of synthesis during DNA replication may be exponential. Differences in the time sequence between the irradiated and control populations of cells of synchronous biological systems will give differences in the ratio of the specific activities of labeled compounds. A review of the results reported on the effects of irradiation on DNA synthesis as measured by labeled precursors suggests the following. The finding of two components of the dose-response curve measured with labeled compounds indicates that irradiation affects more than one process involved in the biosynthesis of DNA. Labeled precursors injected during or shortly after irradiation should give results which should more accurately reflect the effects of irradiation on the DNA synthetic process. Relative changes in the rate of synthesis and relative changes in the population of cells in the irradiated and paired control biological systems make quantitative results between the dose delivered and the effects of DNA synthesis unlikely if the labeled precursors are not administered immediately after irradiation. Labeled precursors injected from several hours up to days after irradiation make the results of the effects of irradiation on DNA synthesis difficult or impossible to evaluate. The finding that DNA synthesis is depressed for days after irradiation probably involves the effects of irradiation on cell processes other than DNA synthesis. Depression of the uptake of the labeled precursors is in all probability an indirect effect mediated through disturbances in other cell processes such as mitosis. It is therefore considered that coordinated biophysical studies on individual cells and biochemical studies on total populations of cells offer one of the best approaches to obtain a better understanding of irradiation effects on DNA. Coordinated in vivo and in vitro studies should be more effective than either study made independently in the attempt to gain a better understanding of the biological effects of irradiation.
- Research Organization:
- Univ. of Virginia, Charlottesville
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-16-026765
- OSTI ID:
- 4796501
- Journal Information:
- Annals of the New York Academy of Sciences, Vol. 95, Issue 2; Other Information: Orig. Receipt Date: 31-DEC-62; ISSN 0077-8923
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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