In thymocytes of C3HA mice carrying the transplantable and ortoaminoazotoluene induced
hepatomas at the time of their intense growth a drastic decrease in
adenosine deaminase activity set in and 3-4-fold augmentation of intracellular concentration of dATP and
dGTP, potential inhibitors of
ribonucleoside diphosphate reductase was observed, leading to the reduction of the
DNA synthesis. The latter event was evidenced by a suppressed 14C-thymidine incorporation into thymocytes
DNA in vitro, decreased
thymidine kinase activity, intracellular
dTTP and depletion of
dCTP pools. Only in the terminal period of hepatocarcinogenesis (12 months) a 4-fold increase in the
corticosterone serum concentration was observed. As for the mice carrying transplantable 22a
hepatoma, serum
hormone levels augmented 4-fold as early as 24 h after
tumor implantation and thereafter kept increased two fold. An elevated activity of
terminal deoxynucleotidyl transferase in mouse thymocytes has been shown to be characteristic of the late periods of
tumor growth reflecting the arrest of the immature cortical thymocyte differentiation. By the time
hepatomas emerged in the course of hepatocarcinogenesis in spleen T and B lymphocytes a significant drop in the activity of
adenosine deaminase (3-4-fold) and
purine nucleoside phosphorylase (2-8-fold) was noted--the events directly correlated with the weakening of cell immune functions. The disorders described were accompanied by the accumulation of
dGTP in spleen T lymphocytes, dATP in B lymphocytes and inhibition of
DNA synthesis, predominantly in T lymphocytes. In the latter instance the pool of
dCTP was found to be depleted. In spleen T and B lymphocytes of mice carrying solid 22a
hepatoma when the peak of its growth was reached (day 5) the rate of
DNA synthesis dropped. Later on (from day 8 to the animal death), however, in spite of the suppression of immune function and the decrease in
adenosine deaminase activity a drastic stimulation of
DNA synthesis in spleen T and B lymphocytes was observed. The increase in spleen T suppressor activity in the course of intense growth of the both types of
hepatomas coincided in the time with the stimulation of the
CTP-dependent
thymidine kinase isoenzyme activity in total T lymphocyte population of the same organ.