THE EFFECTS OF HISTAMINE H₂ RECEPTOR AGONIST,ANTAAGONIST 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 bloed(PBCFU-GM)represents stem and/or progenitor cells from human blood,In this paper,the effects ofhistamine H₂ receptor agonist 4-methylhistamine(4-MH)and its antagonist ranitidine(Ranit) on thegrowth of PB CFU-GM cultured in methylcellulose system were studied and their differential effects onnormal PB CFU-GM and leukemic HL-60 cells were compared with the effect of the antineoplasticagent cytosine arabinoside(Ara-C). It was found that the histamine H₂ receptor agonist 4-MHstimulated the growth of PB CFU-GM when 4-MH was added at the concentrations from 10^-9mol·L^-1 to 10^-6 mol·L^-1 among which the dose 10^-8 mol·L^-1 exerted most potent stimulatingeffect(the PB CFU-GM colony numbers was 137.68%±8. 20%、vs the control,P<0. 01).Incontrast, the antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at theconcentrations 10^-9～10^-5 mol·L^-1 cultured for 14d in the same methylcellulose system, Theinhibition 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, Ranitexerted much greater inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of10^-6mol·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 CFL-GM was 100% at the intensivechemotherapeutic dose of 10^-5 mol·L^-1. It would appear that the histamine H₂ receptor agonist 4-MH possesses stimuiating effect on thegrowth of PB CFU-GM similar to its effect on CFU-GM frorn bone marrow as documented before,Itis suggested that the histamine H₂ receptor antagonist Ranit has,to some extent,potential in thetreatment of myeloid leukemia,especially when combined with antineoplastic agent Ara -C atsuboptimal doses.