Proliferation and differentiation of murine haemopoietic progenitor cells in stroma-free culture in the presence of metabolites of chlorinated pesticides

We have studied the influence of metabolites of chlorinated pesticides (lin dane, pentachlorophenol, hexachlorobenzene) on proliferation and differenti ation in two stroma-free murine bone marrow culture models, a multipotent p rogenitor cell line (FDCP-mix) and primary lineage-depleted bone marrow cel ls. Tetrachlorohydroquinone (Cl(4)pHQ), tetrachloro-p-benzoquinone (Cl(4p)B Q), but not their positional isomers, tetrachlorocatechol (Cl(4)oKQ) and te trachloro-o-benzoquinone (Cl(4)oBQ), nor 2,4,6-trichlorophenol (2,4,6-Cl3P) , were much more toxic to FDCP-mix cells cultured under conditions which le ad to self-renewal than under conditions which lead to granulocyte-macropha ge differentiation. Under the latter conditions, Cl(4p)HQ and Cl(4)pBQ even stimulated growth at intermediate concentration levels. In the primary cel l cultures, pronounced differences were observed in the sensitivity between individual developmental pathways and between the different compounds. The percent of cells differentiating into the granulocytic lineage was increas ed at high concentration levels of each test compound. However, stimulatory effects on the macrophage lineage were observed at intermediate concentrat ion levels of Cl(4p)HQ, Cl(4p)BQ and 2,4,6-Cl3P, and differentiation into e rythrocytes was stimulated at low concentrations of 2,4,6-Cl3P. It is concl uded that chlorinated monocyclic pesticides, after biotransformation to qui noid metabolites, may interact directly with haemopoietic progenitor cells with differential effects on self-renewal and differentiation. These mechan isms could lead to myeloplastic disorders. (C) 2001 Elsevier Science Ltd. A ll rights reserved.