Suppressor cell activity in tumor-bearing mice. II. Inhibition of DNA synthesis and DNA polymerases by TBH splenic suppressor cells
Farrar, W.L.; Elgert, K.D.
Journal of Immunology 120(4): 1354-1361
1978
ISSN/ISBN: 0022-1767 PMID: 305940 Document Number: 125652
Spleen cells from lymphocyte DNA synthesis and polymerase .alpha. activity were always higher than their normal counterparts; upon mitogen stimulation this was reversed. Normal animal spleen cell DNA polymerase .alpha. activity exhibited a direct correlation with mitogen-induced DNA synthesis. In the presence of mitogen, normal spleen cells demonstrated a significant increase in DNA synthesis with a corresponding increase in DNA polymerase .alpha. activity. TBH spleen cells upon mitogen stimulation resulted in a concomitant decrease in DNA synthesis and polymerase activity. Inhibition kinetics revealed that IDP was not a competitive inhibitor of DNA polymerase .alpha. and did not bind directly to the DNA template in the absence of polymerase. The kinetics imply the production of an enzyme-substrate-inhibitor complex which cannot undergo further reaction to yield a normal product. Substances elaborated by tumor-induced suppressor cells operate at a molecular site of DNA polymerases resulting in inhibited cellular proliferation.