The effects of a leukaemia‐controlling dose of acivicin on murine splenic lymphocytes in vitro and in vivo

Summary The development of successful chemotherapy for cancers, including leukaemia, is based on the exploitation of significant toxic differentials of the agents, between the cancer cells and their normal countilerparts. A concentration of 0.1 μmol/L of the amino acid analogue acivicin (L‐(α S.5S)‐α‐amino‐.Vchloro‐4,5‐dihydro‐5‐isoxazoleacetie acid) was sufficient to inhibit [ 3 H]‐DNA synthesis in mitogen stimulated murine splenic lymphocytes and WEHI 7.1 murine loukaemic cells in vitro. at glutamine concentrations up to 0.5 μmol/L. However, al concentrations of glutamine of 1.0 μmol/Land above, more actvicin was required to inhibit WEHI 7.1 cells than to inhibit the splenic lymphovytes. At 1.0 mmol/L glutamine 18 h of exposure to an optimal inhibitory concentration of actvicin (0.5 μmol/L) in vitro was sufficient to inhibit [ 3 H]‐DNA synthesis in the mitogen stimulated lymphocytes. whereas 24 h of exposure to an optimal inhibitory aciviein eoneeniration of 2.0 μmol/L was required for inhibition of [ 3 H]‐DNA synthesis in the WEHI 7.1 leukaemic cells. When an actvicin inoeuhition regime that was sufficient to eontrol the growth of intraperitoneally (i.p. implanted WEHI 7.1 leukaemic cells was administered to Balb/c mice, the primary immune response was significantly inhibited loan anligen given either during orafler the actvicin treatment. These results indicale that lymphocytes replicating in vivo a specific primary immune response eould be as sensitive to actviein as leukaemic cells.