[The negative effect of 4-methylhistamine, an H2 receptor agonist, on cytotoxicity of Ara-C for HL-60 leukemia cells].
OBJECTIVE: To study the effect of 4-methylhistamine on cytotoxicity of Ara-C for HL-60 leukemia cells in vitro. METHODS: Proliferation of HL-60 cells was determined by semi-solid colony culture and 3H-TdR incorporation. The typical NBT reduction was used to check cell differentiation. Intracellular cAMP and calcium concentration were determined by high pressure liquid chromatography(HPLC) and fluorescence method, respectively. RESULTS: When HL-60 cells were pretreated with 10(-8) mol.L-1 4-MH for 24 hrs, the cytotoxicity of Ara-C[10(-8)-10(-4)mol.L-1] for HL-60 leukemia cells was significantly decreased both in liquid and semisolid culture. The result of colony counting indicated that the IC50 for HL-60 cells were 1.68 x 10(-6)mol.L-1 with 4-MH pretreatment nad 2.14 x 10(-8)mol.L-1 without 4-MH pretreatment, respectively. Therefore, the potency of Ara-C was reduced nearly 80 times according to IC50 doses. It is interesting that 10(-6)mol.L-1 ranitidine, an antagonist of H2 receptor, can elaborate the negative effect of 4-MH on cytotoxicity of Ara-C for HL-60 cells. CONCLUSION: The dose of Ara-C should be adequately increased, or Ara-C should be used with H2 receptor antagonist such as ranitidine when treating myeloid leukemia patients.