INHIBITION OF DNA REPLICATION AND GROWTH OF SEVERAL HUMAN AND MURINE NEOPLASTIC CELLS BY APHIDICOLIN WITHOUT DETECTABLE EFFECT ON SYNTHESIS OF IMMUNO GLOBULINS AND HLA ANTIGENS

Aphidicolin inhibits DNA replciation and growth of all tested human and murine neoplastic cells, including leukemic T- and B-lymphocytes and melanocarcinoma cells. The concentration of aphidicolin causing 50% inhibition of DNA synthesis in all of the tested neoplastic cell lines is similar to that necessary to inhibit DNA synthesis in HeLa [human cervical carcinoma] cells by 50%. The mechanism of inhibition of DNA synthesis in neoplastic cells is again due to the inhibition of DNA polymerase .alpha. by aphidicolin. Aphidicolin at a concentration 100 times higher than that causing 50% inhibition of DNA synthesis and cell growth had no effect on total protein synthesis, on the secretion of Ig or on the expression of HLA antigens which are involved in relevant phenomena of the immune response. [The effect of aphidicolin was tested on the growth of the following cultured cell lines: LIK, RAJI and TO 117 (human B-lymphoblastoid cells); MOLT-4 (human T-lymphoblastoid cells); COLO-38 and MAI (human melanoma cell lines); and P3/X63-Ag8 (murine myeloma cell line). The effect of aphidicolin on the expression of HLC antigens was tested on the following Epstein-Barr virus-transformed cells: WT 52, WT 48, TO 116 and TO 117. The effect of aphidicolin on protein synthesis and Ig secretion was studied on the .gamma.1,K-secreting Ig murine myeloma P3/X63 cell line.].