RADIOACTIVE INDICATORS IN BIOCHEMISTRY 983 



of 50 days 70% of the soft bones (epiphysis) and as much as 93% of 

 the hard bones (diaphysis) remained unchanged^^^). No similar experiments 

 were carried out with human subjects but, as the extent of renewal 

 increases only slightly with increasing time, we seem to be justified in 

 concluding that a large part of the mineral constituents of the adult 

 skeleton remains unchanged during life. 



The above-mentioned protection of highly active phosphate apatite 

 layers by slightly active ones much resembles the protection of lead 

 incorporated with the skeleton. From a blood plasma with comparatively 

 high lead content, lead-replacing calcium ions are incorporated with 

 an apatite layer. Since the lead content of the plasma decreases with 

 time, the above-mentioned layer may be covered by others containing 

 only negligible amounts of lead. The probability of an escape of lead 

 from the skeleton is thus strongly reduced. It takes place, however, to 

 some extent over long time intervals, constantly supplying the plasma 

 with toxic lead. Not only lead but also numerous other elements, e.g. 

 uranium,(^^) find more or less permanent abode in the skeleton. 



DETERMINATION OF THE LIFE-CYCLE OF BLOOD CORPUSCLES 



In the determination of the life-time of blood corpuscles, the marked 

 decline of the specific activity of the precursor with time proves to be 

 most advantageous, as shown, for example, in Ottesen's work^*^*") on 

 the life-cycle of nucleated red corpuscles. After administration of labelled 

 phosphate, the specific activity of the inorganic phosphate of the blood 

 plasma declines, as seen in Fig. 5. It takes some time for the inorganic 

 phosphate of the marrow to come into exchange equilibrium with the 

 inorganic phosphate of the plasma, but after that, the specific activity 

 of the marrow inorganic phosphate will markedly decrease with time as 

 well. Thus, the deoxyribonucleic acid molecules formed with partici- 

 pation of labelled inorganic phosphate in the course of the first day are 

 much more active than those formed later. The deoxyribonucleic acid- 

 containing red corpuscles have a definite life-time. As soon as this is 

 reached they are destroyed and their nucleic acid phosphorus, which is 

 now exposed to the effect of phosphatase, is split off and soon lost in 

 the larger pool of inorganic phosphate present in the body. The end of 

 the life-cycle of the red corpuscles will thus be indicated by a sudden 

 decrease in the activity of the deoxyribonucleic acid extracted from the 

 erythrocytes. 



(45)Hevesy, Levi and Rebbe, Biochem. J. 34, 532 (1940). 

 ''«>Neuman and Neuman, J. Biol. Chem. 174, 711 (1948). 

 ^^^""^ Nature 162, 730 (1948); Diss., Copenhagen (1951). 



