Changes in DNA and purine nucleotide synthesis and sensitivity to glucocorticoids in mouse spleen T- and B-lymphocytes coupled with disturbances in differentiation and immune function during tumor growth

Biochemical disturbances in immunocompetent spleen cells (T- and B-lymphocytes) were found during the growth of transplanted and orthoaminoazotoluene-induced solid hepatomas in mice of line C3HA. As soon as the hepatomas appeared during carcinogenesis, a 2- to 6-fold decrease in the adenosine deaminase activity and a 7- to 10-fold drop in the purine nucleoside phosphorylase activity, directly correlated with weakening of the immune function, was found in the T- and B- lymphocytes. These changes were accompanied by a 5.4-fold increase in the dGTP concentration (T-lymphocytes) and a 4.0-fold increase in the dATP concentration (B-lymphocytes) as well as by inhibition of DNA synthesis, primarily in the T-lymphocytes. The pool of dCTP was decreased in both types of cells. In the T- and B-lymphocytes of the spleens of mice carrying transplanted solid hepatoma 22, the decreases in the thymidine kinase activity, the rate of incorporation of labeled thymidine into DNA, and the intracellular dTTP and dCTP concentrations showed that DNA synthesis was inhibited at the time of the maximum rate of tumor growth (5th day). The growth of the hepatoma (beginning with the 8th day and until death of the animals) was subsequently accompanied by sharp stimulation of DNA synthesis in the T-more » and B-lymphocytes of the spleen, despite the weakening of the immune function and the decrease in the adenosine deaminase activity.« less