Cimetidine induced pancytopenia. Effect on human CFU-MIX colony formation.
We describe a 26 year-old male with a pancytopenia possibly due to cimetidine. Using progenitor cell culture techniques we investigated the mechanism of this bone marrow toxicity. Our results show a cimetidine dose-dependent inhibition of normal human CFU-GM colony formation as described by Fitchen and Koeffler in 1980. No differences in growth inhibition were found between the patients' recovery marrow and the controls. Toxicity on normal human CFU-MIX colony formation was, however, far more pronounced. At concentrations as low as 5 micrograms/ml the numbers of CFU-MIX colonies were decreased by almost 20% and more than 30% in cultures of two normal bone marrow samples. A significant decrease in CFU-MIX colony size was measured even at therapeutic levels (0.5 micrograms/ml). No obvious decrease in CFU-GM colony size was noticed at low concentrations. Experiments with T-cell- and monocyte-depleted bone marrow samples gave similar results: a pronounced inhibition of the CFU-MIX colony formation at low concentrations of cimetidine whereas the CFU-GM formation was less affected. It is therefore very unlikely that Accessory cells play part in the cimetidine induced CFU-MIX inhibition. Our results suggest the existence of H2 histamine receptors on human CFU-MIX (= multipotent progenitor cell). Blocking these receptors prevents the multipotent progenitor cell from going into the DNA-synthesis phase of the cell cycle.
Uyttenbroeck
W
W
Laboratory of Experimental Haematology, University of Antwerp, Belgium.
Korthout
M
M
De Bock
R
R
Van Bockstaele
D R
DR
Peetermans
M E
ME
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002927:Cimetidine / Q000009:adverse effects* / Q000633:toxicity; D003114:Colony-Forming Units Assay; D006801:Humans; D008297:Male; D010198:Pancytopenia / Q000139:chemically induced*
D002927:Cimetidine