The effects of benzene and other leukaemogenic agents on haematopoietic stem and progenitor cell differentiation

Eur J Haematol Suppl. 1996:60:119-24. doi: 10.1111/j.1600-0609.1996.tb01657.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Benzene / toxicity*
  • Carcinogens / toxicity*
  • Cell Differentiation / drug effects
  • Cytokines / physiology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Leukemia / chemically induced*
  • Leukemia / pathology
  • Leukemia / physiopathology
  • Leukemia, Experimental / chemically induced*
  • Leukemia, Experimental / pathology
  • Leukemia, Experimental / physiopathology

Substances

  • Carcinogens
  • Cytokines
  • Benzene