[The effects of histamine H2 receptor agonist, antagonist and antineoplastic agent on the in vitro growth of PB CFU-GM from normal individuals and HL-60 leukemia cells].
Colony forming unit of granulocytes and macrophages from peripheral blood (PB CFU-GM) represents stem and/or progenitor cells from human blood. In this paper, the effects of histamine H2 receptor agonist 4-methylhistamine (4-MH) and its antagonist ranitidine (Ranit) on the growth of PB CFU-GM cultured in methylcellulose system were studied and their differential effects on normal PB CFU-GM and leukemic HL-60 cells were compared with the effect of the antineoplastic agent cytosine arabinoside (Ara-C). It was found that the histamine H2 receptor agonist 4-MH stimulated the growth of PB CFU-GM when 4-MH was added at the concentrations from 10(-9) mol.L-1 to 10(-6) mol.L-1 among which the dose 10(-8) mol.L-1 exerted most potent stimulating effect (the PB CFU-GM colony numbers was 137.68% +/- 8.20% vs the control, P < 0.01). In contrast, the antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at the concentrations 10(-9)-10(-5) mol.L-1 cultured for 14 d in the same methylcellulose system. The inhibition rate was 23.73% +/- 1.16% (10(-9) mol.L-1) and 41.42% +/- 6.75% (10(-6) mol.L-1), respectively. Although both Ranit and Ara-C could inhibit the growth of PB CFU-GM in vitro, Ranit exerted much greater inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of 10(-6) mol.L-1 (100% inhibition for HL-60 and < 50% inhibition for PB CFU-GM). However, the inhibition rate of Ara-C for both HL-60 and PB CFU-GM was 100% at the intensive chemotherapeutic dose of 10(-5) mol.L-1. It would appear that the histamine H2 receptor agonist 4-MH possesses stimulating effect on the growth of PB CFU-GM similar to its effect on CFU-GM from bone marrow as documented before. It is suggested that the histamine H2 receptor antagonist Ranit has, to some extent, potential in the treatment of myeloid leukemia, especially when combined with antineoplastic agent Ara-C at suboptimal doses.
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Research Laboratory of Blood Physiology, Human Medical University, Changsha.
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D017442:Histamine Agonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008761:Methylhistamines / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D008761:Methylhistamines; D003561:Cytarabine; D011899:Ranitidine