The incorporation of thymidine (thymine deoxyriboside) into deoxyribonucleic acid (DNA) of proliferating cells has been studied in the past with various isotopic labels and biochemical techniques. Reichard and Estborn showed that thymidine-N15 was a specific precursor of DNA thymine in rats (1). Friedkin, Tilson, Roberts and Wood (2, 3) used thymidine-2-CI4 to show that this compound was incorporated into DNA thymidine of proliferating embryo and animal tissues with negligible partition of radioactivity into other components of DNA or into ribonucleic acid.The recent synthesis of tritium-labeled thymidine by Taylor, Woods and Hughes (4) and in vitro by serial autoradiographic evaluation of labeled cell populations (6-9). In the course of these in vivo investigations it became important to assess the availability time of tritiated thymidine for incorporation into DNA following rapid intravenous injection. It is essential for serial study of proliferating cell populations that the H3-thymidine label be available for incorporation into new DNA for only a small part of the DNA synthesis time, and that afterward there be no further label availability. This short availability time of H3-thymidine then permits study of the various components of the generation cycles (preand postmitotic rests, mitosis and DNA synthesis) by serial study of the appearance of labeled mitotic figures, the appearance of labeled nondividing cells and the decrease of labeling upon subsequent successive mitoses. From these data a kinetic analysis should determine the flow rate between compartments and the time spent in each state (8,9).The metabolic studies reported here indicate that the effective availability time for intravenously administered H3-thymidine is a matter of minutes. The metabolic fate of this tritium-labeled compound was examined by analyses of serial specimens of plasma, stool and urine as well as by evaluation of autoradiograms of tissues. These studies revealed that catabolism of some H3-thymidine to tritiated water (THO) as well as to nonvolatile tritiated compounds occurs. From the data to be presented here it appears that at least 50 per cent of injected H3-thymidine was retained in vivo and was presumably incorporated into new DNA of proliferating cells.
Tissues in the adult can be divided into two categories, one of which is being replaced continually and one in which the cell populations remain esientially stable throughout adult 1ife.l The possible relationship between neoplasia and the rate of cellular turnover in tissues has not been explored satisfactorily, although this problem, particularly with neoplasia of the hematopoietic tissue, has received considerable attention. T o Virchow, leukemia was a result of an increased and uncontrolled proliferation of cells resulting in local invasion and distant metastask2 Ultimately the tumor cells became a parasitic burden to the host, and death ensued. There can be no doubt that in some respects Virchow's concept is essentially correct. However, Biernian3 has felt that certain types of leukemia might well result from a defect in the removal system, and he proposed a balance hypothesis for neoplasia, particularly the leukemias. The resolution of these differences becomes of great importance because, on the one hand, therapy might well be aimed a t the control of new cell proliferation and, on the other hand, a t correcting a faulty removal mechanism.In order to understand better the mechanisms of neoplasia, an understanding of the processes of normal cell proliferation and removal is essential. A great amount of effort has been devoted to the study, by various techniques and in various species, of the characteristics of proliferation of the different hematopoietic cell systems from the stem forms to the mature elements. Classic techniques used have included marrow suppression by radiation or chemical compoundsI4~ mitotic counts and cell enumeration in lymph nodes,'j cross-circulation experiment^,^^ parabiosis,*s transfusions,'O# arteriovenous catheterization and cross circulation,12 cell and nucleus volume measu r e m e n t~,~~' cannulation of the lymphatic cell labeling with dyes,l7-I9 in vitro cell culture,20-23 and leukocyte depletion 26 Labeling with radioactive or stable isotopes combined with the classic techniques resulted in significant progress in this area. Outstanding is the classic work in which the life span of human erythrocytes was determined to be 120 days.26 Other isotopic methods employed to study the several hematopoietic cell systems include the tagging27-31 of desoxyribonucleic acid (DNA)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.