Inhibitors of DNA synthesis produced by herpesvirus-transformed cell lines.

Inhibitory factors were detected in the supernatant fluids of two herpesvirus-transformed lymphoid cell lines, one a B cell line established from a cotton-topped marmoset with EBV-induced lymphoma (1605L) and the other a HVS-transformed marmoset T cell line (C-1 Ax). The factors produced by both cell lines inhibited the uptake of 125I-iododeoxyuridine (125I-IUDR) by lymphocytes stimulated by both phytohemagglutinin and pokeweed mitogen. Both factors also suppressed the uptake of 125I-IUDR by cells of lymphoid cell lines of both B and T cell origin, indicating that neither factor was specific for lymphoid subpopulations. Furthermore, the factor produced by the 1605L cell line did not exhibit tissue specificity in the target cells that it affected, since it also suppressed 125I-IUDR uptake by the HEp-2 cell line, which is epithelial. Antibody-dependent cellular cytotoxicity, an assay that has been reported to require effector cells capable of protein synthesis but not DNA synthesis, was not suppressed by either factor, indicating that these inhibitors acted at the level of DNA synthesis. Experiments investigating the kinetics of the inhibition of PHA blastogenesis by the 1605L factor suggested that this inhibitor blocked an early stage in the DNA synthetic cycle, since maximum inhibition was observed only when the factor was present early in the culture period.