[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.


CONCLUSIONS
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.
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Research Laboratory of Blood Physiology, Hunan Medical University, Changsha 410078.
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology*; D018922:HL-60 Cells / Q000473:pathology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006801:Humans; D008761:Methylhistamines / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D017442:Histamine Agonists; D008761:Methylhistamines; D003561:Cytarabine; C025566:4-methylhistamine; D000242:Cyclic AMP; D002118:Calcium