Inhibition of human bone marrow-derived stem cell colony formation (CFU-E, BFU-E, and CFU-GM) following in vitro exposure to organophosphates.
Cholinergic toxicity of organophosphate insecticides is regarded as the principal health hazard associated with both human and animal exposures. Recent studies indicate that these pesticides may have important effects on both the immune and hematopoietic systems. In the present study, human bone marrow cells were exposed in vitro to paraoxon and malaoxon (the primary metabolites of parathion and malathion). These compounds produced dose-dependent depression of colony formation by erythrocyte (burst-forming units-erythroid [BFU-E] and colony-forming units-erythroid [CFU-E]) and granulocyte-macrophage progenitors (colony-forming units-granulocyte-macrophage [CFU-GM]). CFU-E colony formation was reduced 15%-57%, by both paraoxon and malaoxon, in the range of 10(-8)-10(-5) M. No effects were seen at 10(-9) and 10(-10) M. Colony formation by BFU-E was reduced 15%-75%, at 10(-9)-10(-5) M organophosphate (OP), then returned to normal at 10(-10) M OP. In comparison to CFU-E, BFU-E appeared to be more sensitive to the suppressive action of OPs. Numbers of CFU-GM colonies were reduced 16%-59% in the range of 10(-9)-10(-5) M OP, then returned to normal at 10(-10) M OP. Choline chloride added to marrow cultures (final concentration, 10 mM) enhanced CFU-GM colony formation at all concentrations of paraoxon and malaoxon. Our results provide a rationale for assessing hematologic parameters in occupationally exposed individuals, and indicate the need to determine both the mechanism and the environmental health consequences of the observed hematopoietic effects.
Gallicchio
V S
VS
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
Casale
G P
GP
Watts
T
T
D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008294:Malathion / Q000031:analogs & derivatives* / Q000633:toxicity; D010261:Paraoxon / Q000633:toxicity*
C100082:malaoxon; D010261:Paraoxon; D008294:Malathion