[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.