The effects of benzene and other leukaemogenic agents on haematopoietic stem and progenitor cell differentiation.
A characteristic shared by a diverse group of myelotoxic compounds and leukaemogens is the ability to act synergistically with granulocyte-macrophage colony stimulating factor (GM-CSF) in increasing clonogenic response. Pretreatment of murine or human bone marrow cells with the benzene metabolite, hydroquinone, but not phenol, catechol or trans, trans-muconaldehyde, results in a selective enhancement of GM-CSF but not an interleukin-3 (IL-3)-mediated clonogenic response. Clonal enhancement is preserved and magnified in enriched populations of CD34+ cells (> 95% purity), suggesting an intrinsic effect on haematopoietic progenitor cell (HPC) recruitment rather than a secondary effect involving accessory cytokines. Clonogenic enhancement of murine HPCs is not accompanied by alterations in GM-CSF receptor expression or ligand affinity and appears to be mediated via a p53-independent mechanism. These observations suggest that hydroquinone treatment alters recruitment and differentiation in a primitive subpopulation of CD34+ cells and are consistent with a role for altered stem cell differentiation in the development of chemically induced myelodysplasias.
Irons
R D
RD
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA. Richard.Irons@UCHSC.EDU
Stillman
W S
WS
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007942:Leukemia, Experimental / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
D002273:Carcinogens; D016207:Cytokines; D001554:Benzene