IN-VITRO EFFECTS OF HYDROQUINONE, BENZOQUINONE, AND DOXORUBICIN ON MOUSE AND HUMAN BONE-MARROW CELLS AT PHYSIOLOGICAL OXYGEN PARTIAL-PRESSURE

A comparative study was undertaken in order to assess the hematotoxic effects of hydroquinone (HQ), 1,4-benzoquinone (BQ), and doxorubicin ( DX) on mouse and human bone marrow (BM) cells. Initial experiments ind icated that the inhibitory effects of near-ambient pO(2) and HQ on gra nulocyte/macrophage colony-stimulating factor (GM-CSF)-induced colony formation were additive. Thus, subsequent experiments were done under conditions of continuous toxicant exposure in complete medium at physi ological temperature and O-2 partial pressure. Viability was measured 24 hr after exposure, and at the concentrations tested, HQ was less cy totoxic than BQ. DX did not exhibit significant cytotoxicity at the co ncentrations used. Both HQ and BQ were slightly more cytotoxic to mous e BM cells than to human BM cells. Dose-response analyses of HQ, BQ, o r DX inhibition of GM-CSF-induced proliferative and colony forming res ponses indicated that murine GM progenitors were significantly less se nsitive to HQ than to the majority of myeloid BM cells that proliferat ed in response to GM-CSF. This preferential resistance of GM progenito rs to HQ was not observed when human BM cells were used. HQ was somewh at more inhibitory to human than to mouse GM-CSF responses. Inhibition of GM-CSF-induced responses by BQ correlated closely with cytotoxicit y, and DX was 1000-fold more inhibitory to GM-CSF-induced proliferativ e and colony-forming responses than either HQ or BQ. Again, DX appeare d to be slightly more inhibitory to human BM cells than to mouse BM ce lls. Purified human hematopoietic progenitor cells (HPCs) were also us ed in the dose-response analyses of HQ, BQ, or DX inhibition of GM-CSF -induced proliferative and colony-forming responses. Inhibition of GM- CSF-induced HPC responses by HQ, BQ, and DX was very similar to that o btained when BM mononuclear cells were used, suggesting that the human HPC is a target for the direct effects of HQ, BQ, and DX. (C) 1994 Ac ademic Press, Inc.