[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes]

Biokhimiia. 1986 Apr;51(4):635-43.
[Article in Russian]

Abstract

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.

Publication types

  • English Abstract

MeSH terms

  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors
  • Animals
  • Antibody-Producing Cells / immunology
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • DNA, Neoplasm / biosynthesis*
  • Drug Resistance
  • Glucocorticoids / pharmacology*
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / immunology
  • Liver Neoplasms, Experimental / metabolism*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Purine Nucleotides / biosynthesis*
  • Purine-Nucleoside Phosphorylase / antagonists & inhibitors
  • Purine-Nucleoside Phosphorylase / metabolism
  • Spleen / enzymology
  • Spleen / immunology
  • Spleen / metabolism*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Thymidine / metabolism
  • Thymidine Kinase / antagonists & inhibitors
  • Thymidine Kinase / metabolism
  • Time Factors

Substances

  • Adenosine Deaminase Inhibitors
  • DNA, Neoplasm
  • Glucocorticoids
  • Purine Nucleotides
  • Purine-Nucleoside Phosphorylase
  • Thymidine Kinase
  • Adenosine Deaminase
  • Thymidine