Skip to main content
SpringerLink
Log in

Kinetics of isotope incorporation into the desoxyribonucleic acid (DNA) of tissues: Life span and generation time of cells

  • Published:
The bulletin of mathematical biophysics Aims and scope Submit manuscript

Abstract

The dynamics of cell multiplication and differentiation in tissues in asteady state and the kinetics of isotope incorporation into the DNA have been theoretically analyzed. Equations have been derived, with the aid of which thegeneration time, thelife span, and the distribution or rate of death of the cells can be obtained if the tissue is in asteady state, i.e., if the number of cells is maintained constant by constant, equal rates of cell division and cell death and if the mean DNA content per cell is also constant. An equation has also been derived which gives thegeneration time in the case of logarithmic multiplication of cells.

Two special cases have been analyzed: InCase 1, the isotope is considered as being introduced into the metabolic system at zero time only; inCase 2, the specific activity of the DNA precursor is considered as being maintained constant. The use of the method has been illustrated by an example in which thegeneration time and themean, themedian, and themode life span, as well as the curve of the rate of death of leukocytes in a patient with chronic leukemic granulocytic leukemia, have been obtained from the rate of P32 incorporation into the DNA.

The merits and the limitations of the method are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literature

  • Barton, A. D. 1954. “Evidence for the Biochemical Stability of Desoxyribosenucleic Acid (DNA).”Federation Proc.,13, 422.

    Google Scholar 

  • Boivin, André, Roger Vendrely, and Colette Vendrely. 1948. “L’acide désoxyribonucléique du noyau cellulaire, dépositaire des caractères héréditaires; arguments d’ordre analytique.”Compt. rend. Acad. sc.,226, 1061–63.

    Google Scholar 

  • Brown, George Bosworth, and Paul M. Roll. 1955. “Biosynthesis of Nucleic Acids.”The Nucleic Acids II, pp. 341–92. (Ed. Chargaff, Erwin, and J. N. Davidson) New York: Academic Press Inc.

    Google Scholar 

  • Brues, Austin M., Marjorie M. Tracy, and Waldo E. Cohn. 1944. “Nucleic Acids of Rat Liver and Hepatoma: Their Metabolic Turnover in Relation to Growth.”Jour. Biol. Chem.,155, 619–33.

    Google Scholar 

  • Christensen, B. Chr., and J. Ottesen. 1955. “The Age of Leukocytes in the Blood Stream of Patients with Chronic Lymphatic Leukemia.”Acta Haematol.,13, 289–98.

    Google Scholar 

  • Craddock, Charles G., Jr., Seymour Perry, and John S. Lawrence. 1956. “The Dynamics of Leukopoiesis and Leukocytosis, as Studied by Leukopheresis and Isotopic Techniques.”Jour. Clin. Invest.,XXXV, 285–96.

    Google Scholar 

  • Cramér, Harald. 1946.Mathematical Methods of Statistics. Princeton, N. J.: Princeton University Press.

    MATH  Google Scholar 

  • Daoust, R., C. P. Leblond, N. J. Nadler, and M. Enesco. 1956. “Rates of Deoxyribonucleic Acid Formation and Cell Production in Regenerating Rat Liver.”Jour. Biol. Chem. 221, 727–33.

    Google Scholar 

  • Deming, W. Edwards. 1943.Statistical Adjustment of Data. New York: John Wiley & Sons, Inc.

    MATH  Google Scholar 

  • Fresco, Jacques R., Aaron Bendich, and Percy J. Russell, Jr. 1955. “Metabolic Stability of Deoxyribonucleic acid (DNA) in Nongrowing Tissue.”Federation Proc.,14, 214.

    Google Scholar 

  • Furst, Sidney S., and George Bosworth Brown. 1951. “On the Role of Glycine and Adenine as Precursors of Nucleic Acid Purines.”Jour. Biol. Chem.,191 239–47.

    Google Scholar 

  • Hamilton, L. D. 1956. “Nucleic Acid Turnover Studies in Human Leukaemic Cells and the Function of Lymphocytes.”Nature,178, 597–99.

    Article  Google Scholar 

  • Hamilton, L. D. 1957. “Metabolic Stability of PNA and DNA in Human Leukemic Leukocytes; The Function of Lymphocytes.” TheLeukemias: Etiology, Pathophysiology and Treatment, pp. 381–400. (Ed. John W. Rebuck, Frank H. Bethel, and Raymond W. Monto) New York: Academic Press Inc.

    Google Scholar 

  • Healy, G. M., L. Siminovitch, R. C. Parker, and A. F. Graham. 1956. “Conservation of Desoxyribonucleic Acid Phosphorus in Animal Cells PropagatedIn Vitro.”Biochim. et Biophys. Acta,20, 425–26.

    Article  Google Scholar 

  • Hershey, A. D. 1954. “Conservation of Nucleic Acids during Bacterial Growth.”Jour. Gen. Physiol. 38, 145–48.

    Article  Google Scholar 

  • Hevesy, G., and J. Ottesen. 1943. “Rate of Formation of Nucleic Acid in the Organs of the Rat.”Acta Physiol. Scand. 5, 237–47.

    Google Scholar 

  • Howard, Alma, and S. R. Pelc. 1951. “Nuclear Incorporation of P32 as Demonstrated by Autoradiographs.”Exptl. Cell Research,2, 178–87.

    Article  Google Scholar 

  • Kline, Daniel L., and Eugene E. Cliffton. 1952a. “The Life Span of Leucocytes in the Human.”Science,115, 9–11.

    Google Scholar 

  • — and Eugene E. Cliffton. 1952b. “Lifespan of Leucocytes in Man.”Jour. Appl. Physiol.,5, 79–84.

    Google Scholar 

  • Leblond, C. P., and Bruce E. Walker. 1956. “Renewal of Cell Populations.”Physiol. Revs. 36, 255–76.

    Google Scholar 

  • Li, Jonah G., and Edwin E. Osgood. 1949. “A Method for the Rapid Separation of Leukocytes and Nucleated Erythrocytes from Blood or Marrow with a Phytohemagglutinin from Red Beans (Phaseolus Vulgaris).”Blood,IV, 670–75.

    Google Scholar 

  • Margenau, Henry, and George Moseley Murphy. 1956. Sec. Ed. “The Mathematics of Physics and Chemistry.” Princeton, N. J.: D. Van Nostrand Company, Inc.

    MATH  Google Scholar 

  • Mirsky, A. E., and Ris, Hans. 1949. “Variable and Constant Components of Chromosomes.”Nature,163, 666–67.

    Google Scholar 

  • Nieset, Robert T. 1955. “Applications of Radioactive Isotopes to Measurements.”Science,122, 742–45.

    Google Scholar 

  • Nygaard, Oddvar, and Harold P. Rusch. 1955. “Incorporation of Radioactive Phosphate into Nucleic Acids of Regenerating Rat Liver.”Cancer Research 15, 240–45.

    Google Scholar 

  • Osgood, Edwin E. 1953. “Drug Induced Hypoplastic Anemias and Related Syndromes.”Ann. Internal Med.,39, 1173–88.

    Google Scholar 

  • — 1954. “Number and Distribution of Human Hemic Cells.”Blood,IX, 1141–54.

    Google Scholar 

  • — 1957. “A Unifying Concept of the Etiology of the Leukemias, Lymphomas, and Cancers.”Jour. Natl. Cancer Inst. 18, 155–66.

    Google Scholar 

  • — and John H. Brooke. 1955. “Continuous Tissue Culture of Leukocytes from Human Leukemic Bloods by Application of ‘Gradient’ Principles.”Blood 10, 1010–22.

    Google Scholar 

  • —, Jonah G. Li, Harold Tivey, Marie L. Duerst, and Arthur J. Seaman. 1951. “Growth of Human Leukemic Leukocytesin Vitro andin Vivo as Measured by Uptake of P32 in Desoxyribose Nucleic Acid.”Science,114, 95–98.

    Google Scholar 

  • —, A. J. Seaman, H. Tivey, and D. A. Rigas. 1954. “Duration of Life and of the Different Stages of Maturation of Normal and Leukemic Leukocytes.”Revue hématol. 9, 543–54.

    Google Scholar 

  • — and Harold Tivey. 1950. “The Biological Half-Life of Radioactive Phosphorus in the Blood of Patients with Leukemia. II. Plasma—with Deviations of Observations from Predicted Values and an Estimate of Total-Phosphorus Turnover Rate.”Cancer,3, 1003–9.

    Article  Google Scholar 

  • —, Harold Tivey, Kenneth B. Davison, Arthur J. Seaman, and Jonah G. Li. 1952. “The Relative Rates of Formation of New Leukocytes in Patients with Acute and Chronic Leukemias.”Cancer,5, 331–35.

    Article  Google Scholar 

  • Ottesen, J. 1954. “On the Age of Human White Cells in Peripheral Blood.”Acta Physiol. Scand.,32, 75–93.

    Article  Google Scholar 

  • Patt, Harvey M. 1957. “A Consideration of Myeloid-Erythroid Balance in Man.”Blood,12, In Press.

  • Rigas, Demetrios A., and Edwin E. Osgood. 1955. “Purification and Properties of the Phytohemagglutinin of Phaseolus Vulgaris.”Jour. Biol. Chem.,212, 607–15.

    Google Scholar 

  • —, Marie L. Duerst, Margaret E. Jump, and Edwin E. Osgood. 1956. “The Nucleic Acids and Other Phosphorus Compounds of Human Leukemic Leukocytes: Relation to Cell Maturity.”Jour. Lab. Clin. Med.,48, 356–78.

    Google Scholar 

  • Ris, Hans. 1947. “The Composition of Chromosomes During Mitosis and Meiosis.”Cold Spring Harbor Symp. on Quan. Biol.,XII, 158–60.

    Google Scholar 

  • Smellie, R. M. S. 1955. “The Metabolism of the Nucleic Acids.”The Nucleic Acids II, pp. 393–434. (Ed. Chargaff, Erwin, and J. N. Davidson) New York: Academic Press, Inc.

    Google Scholar 

  • Stevens, Catherine E., R. Daoust, and C. P. Leblond. 1953. “Rate of Synthesis of Desoxyribonucleic Acid and Mitotic Rate in Liver and Intestine.”Jour. Biol. Chem. 202, 177–86.

    Google Scholar 

  • Swick, Robert W., Arthur L. Koch, and Dorothy M. Tahara. 1955. “Stability of DNA during growth.”Federation Proc. 14, 149.

    Google Scholar 

  • Takagi, Yasuyuki, Liselotte I. Hecht, and Van R. Potter. 1956 “Nucleic Acid Metabolism in Regenerating Rat Liver. II. Studies on Growing Rats.”Cancer Research,16, 994–98.

    Google Scholar 

  • Taylor, Herbert J., Philip S. Woods, and Walter L. Hughes. 1957. “The Organization and Duplication of Chromosomes as Revealed by Autoradiographic Studies using Tritium-Labeled Thymidine.”Proc. Natl. Acad. Sci. U.S.A. 43, 122–28.

    Article  Google Scholar 

  • Thorell, Bo. 1955. “Nucleic Acids in Chromosomes and Mitotic Division.”The Nucleic Acids II, pp. 181–98. (Ed. J. N. Chargaff, and J. N. Davidson) New York: Academic Press Inc.

    Google Scholar 

  • Vendrely, R. 1955. “The Deoxyribonucleic Acid Content of the Nucleus.”The Nucleic Acids II, pp. 155–80. (Ed. Chargaff, Erwin, and J. N. Davidson) New York: Academic Press, Inc.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Experimental Medicine, University of Oregon Medical School, Portland, Oregon

    Demetrios A. Rigas

Authors
  1. Demetrios A. Rigas
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Aided in part by grant C-2350 from the National Institutes of Health, U. S. Public Health Service, and contract AT(45-1)-581 from the U. S. Atomic Energy Commission.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rigas, D.A. Kinetics of isotope incorporation into the desoxyribonucleic acid (DNA) of tissues: Life span and generation time of cells. Bulletin of Mathematical Biophysics 20, 33–70 (1958). https://doi.org/10.1007/BF02476560

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02476560

Keywords

Search

Navigation