Zinc porphyrins: potent inhibitors of hematopoieses in animal and human bone marrow.
The effects of selected heme analogues on heme oxygenase activity in tissues and on human and rabbit bone marrow hematopoietic colony growth were examined. Zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP), at concentrations ranging between 1 and 20 microM, produced significant inhibition of human and rabbit bone marrow erythroid (CFU-E, BFU-E) and myeloid (CFU-GM) colony growth. The growth inhibition produced by 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 mesoporphyrin 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 heme oxygenase were demonstrated. Chromium mesoporphyrin administered intravenously proved lethal to animals. These results indicate that exposure of bone marrow to ZnPP and ZnMP can be deleterious to hematopoietic cells and raise the possibility that ZnPP, which is endogenously formed and found in high concentration in red blood cells in lead-poisoned children, may itself participate in the bone marrow toxicity produced by this metal.
Lutton
J D
JD
The Rockefeller University Hospital, New York, NY 10021, USA.
Abraham
N G
NG
Drummond
G S
GS
Levere
R D
RD
Kappas
A
A
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D002857:Chromium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D011817:Rabbits; D013045:Species Specificity; D014001:Tin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D002857:Chromium; D004921:Erythropoietin; C017803:zinc protoporphyrin; D014001:Tin; C058069:zinc mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D015032:Zinc