ZINC PORPHYRINS - POTENT INHIBITORS OF HEMATOPOIESES IN ANIMAL AND HUMAN BONE-MARROW

The effects of selected heme analogues on heme oxygenase activity in t issues and on human and rabbit bone marrow hematopoietic colony growth were examined, Zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnM P), at concentrations ranging between 1 and 20 mu M, produced signific ant inhibition of human and rabbit bone marrow erythroid (CFU-E, BFU-E ) and myeloid (CFU-GM) colony growth, The growth inhibition produced b y ZnPP or ZnMP was not overcome with exposure of cultures to elevated levels of the growth factors erythropoietin and granulocyte-macrophage colony stimulating factor. In contrast, tin protoporphyrin and tin me soporphyrin did not display any significant bone marrow toxicity when used at similar concentrations, In other studies, differential effects of tin mesoporphyrin and ZnMP administered intravenously on kidney he me oxygenase were demonstrated, Chromium mesoporphyrin administered in travenously proved lethal to animals. These results indicate that expo sure of bone marrow to ZnPP and ZnMP can be deleterious to hematopoiet ic cells and raise the possibility that ZnPP, which is endogenously fo rmed and found in high concentration in red blood cells in lead-poison ed children, may itself participate in the bone marrow toxicity produc ed by this metal.