Modulation of Stromal Cell Function in DBA/2J and B6C3F1 Mice Exposed to Benzene or Phenol

Inbred B6C3F1 (B6) mice are more resistant to benzene myelotoxicity than are inbred DBA/2J (D2) mice. This difference may be due to increased sensitivity of the hemopoietic microenvironment in D2 mice to benzene or benzene metabolites relative to B6 mice. The objectives of this investigation were to determine whether stromal cells which support hemopoiesis in the marrow were more sensitive to benzene in D2 mice than in B6 mice and to determine whether these strains would continue to express differences in susceptibility to phenol, an oxidative metabolite of benzene. Mice were given benzene (100 mg/kg) or phenol (100 mg/kg) intraperitoneally, twice a day for four consecutive days. On Day 5 marrow cell suspensions were removed from mice given benzene or phenol and from controls, plated in culture and assayed for (1) the relative number of adherent stromal cell (ASC) colonies present, (2) the number of granulocyte/monocyte precursors from benzene or phenol treated mice that could be supported by ASC from normal mice in coculture, and (3) the number of granulocyte/monocyte precursors from normal mice which could be supported by ASC from benzene or phenol treated mice. After benzene administration, only reductions in body weight and marrow cellularity followed the expected pattern and were reduced to a greater extent among D2 mice than B6 mice. Benzene had no significant effect on ASC colonies or on the number of granulocyte/monocyte precursors present. In contrast, the ability of ASC to support hemopoiesis of granulocyte/monocytes from normal donors was reduced to a greater degree among B6 mice than among D2 mice which paradoxically showed an increase in the ability to support hemopoiesis in coculture. Phenol significantly reduced the ability of ASC to support hemopoiesis of granulocyte/monocyte precursors but no preferential effect between strains was evident. These results suggest that benzene, but not phenol, is metabolized differently between the two strains and that bone marrow stromal cells, components of the hemopoietic microenvironment, are sensitive targets for benzene or its oxidative metabolites.