ERYTHROID PROGENITOR CELLS THAT SURVIVE BENZENE EXPOSURE EXHIBIT GREATER RESISTANCE TO THE TOXIC BENZENE METABOLITES BENZOQUINONE AND HYDROQUINONE

Benzene is a well known hematotoxicant which induces hematopoietic dys crasias of varying intensities in different individuals and even in di fferent strains of the same experimental animal species. Although ther e is ample evidence that diverse responses to benzene are related to d ifferences in benzene metabolism, we have recently provided evidence i mplicating differences in host target cell susceptibility to these div erse responses to benzene. The present study extends our previous work and concerns strain-specific differences in marrow progenitor cells t hat survive benzene exposure. Two mouse strains (Swiss-Webster and C57 B1/6J) which respond to benzene exposure with different intensities of bone marrow cytotoxicity were used. Bone marrow cells from benzene-ex posed and untreated mice were cultured with one of five benzene metabo lites: 1,4-benzoquinone (BQ), catechol (C), hydroquinone (HQ), muconic acid (MA) or phenol (P) and the abilities of these cells to produce e rythroid (CFU-e) or granulocyte/macrophage colonies (GM-CFU-c) were as sessed. In both strains, marrow cells isolated from benzene-exposed mi ce showed a higher percentage of plated CFU-e surviving culture with B Q, HQ or MA than marrow cells isolated from control mice. In contrast, bath strains of benzene-exposed mice displayed decreased percentages of plated CFU-e surviving culture with catechol than cells isolated fr om control mice. Only one condition (the culturing of cells with HQ un der GM-CFU-c forming conditions) showed any strain-specific difference in plating efficiency. In all, 20 possible combinations of benzene me tabolites and cell types were examined (5 metabolites x 2 progenitor c ell types x 2 strains). With seven of these combinations, the colony-f orming efficiencies were higher for plated cells isolated from benzene -exposed mice than from untreated mice. With three combinations, the c olony-forming efficiencies were lower for cells from benzene-exposed m ice, and for ten combinations, there were no changes in plating effici encies. Possible mechanisms for an acquired resistance to the toxiciti es of benzene metabolites were explored by measuring the concentration s of hepatic and bone marrow sulfhydryl (SH) groups in cells isolated from benzene-exposed and untreated mice. In both strains, benzene expo sure induced no changes in hepatic SH concentrations, but the SH conte nt of bone marrow was more than doubled after benzene exposure in both strains. These results suggest that a fraction of hematopoietic proge nitor cells are able to survive severe benzene exposure and produce pr ogeny because of a marked increase in marrow SH groups which react wit h electrophilic benzene metabolites. Moreover, this protective mechani sm occurs in two mouse strains with differing susceptibilities to benz ene.