194 CELLULAR METABOLISM 



found in transplantable mammary carcinomas that, whereas 4000 r pro- 

 duced a mean reduction of 5.4 per cent in the desoxyribonucleic acid 

 content per cell, 2000 r caused no significant changes — the question 

 would still remain whether a decrease in the nucleic acid content due 

 to irradiation should be explained by a diminution in the rate of for- 

 mation of nucleic acid molecules or by degradation of some of the nu- 

 cleic acid molecules present. Istopic indicators make it possible to dis- 

 tinguish between new and old molecules, and the experiments show that 

 it is mainly the rate of formation of new molecules which is diminished 

 by the action of ionizing radiation. 



Investigations comparing P^^ content of desoxyribonucleic acid and of 

 inorganic phosphates in various tissues after administration of labeled 

 phosphate clearly indicate a close connection between incorporation of 

 P^- into desoxyribonucleic acid of the tissue and cell division. Only 

 minute amounts of P^^ were found in the desoxyribonucleic acid of or- 

 gans which showed a very low mitotic index, such as the liver and kidney 

 of grown rats. On the other hand a marked P^^ content was found in 

 the desoxyribonucleic acid of corresponding organs of newly born ani- 

 mals or in the liver of the partially regenerating hepatectomized adult 

 rat (22). Similar results were demonstrated in investigations in which 

 the incorporation of N^^ into desoxyribonucleic acid was studied (23, 

 24a). In organs of adult animals which show a high percentage of mi- 

 totic figures, such as the bone marrow, the intestinal mucosa, or the 

 spleen, the desoxyribonucleic acid has been found to take up an appreci- 

 able fraction of the admistered labeled phosphate (25). It is also of 

 interest to note that the desoxyribonucleic acid P of white corpuscles 

 (26) and nucleated erythrocytes (27) in which mitosis is absent does not 

 interchange with P^^ present in the circulation. 



In these investigations the desoxyribonucleic acid was isolated from 

 the total organ or from the total nuclei of the organ, and its P^^ or its 

 N^^ content determined. Such investigations did not reveal the phase 

 of the mitotic cycle wherein the incorporation of P^^ into the desoxy- 

 ribonucleic acid molecule actually occurs. In some preliminary work 

 utilizing Jensen rat sarcoma, however, P^^ intake was measured and 

 also the cells in mitosis were counted. These experiments indicated, 1 

 hr after irradiation, when nucleic acid synthesis was observed to be 

 minimal, that most of the cells found in mitosis (almost all the mitoses 

 were abnormal) must have formed their nucleic acid before irradiation 

 (17). Further information on the above point can be obtained by using 

 autoradiographs as a cytochemical tool, as was done by Howard and 

 Pelc (28). These experimenters have grown roots of Vicia faba for 

 periods of 2-48 hr in solutions containing labeled sodium phosphate. 



