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 dyscrasias of varying intensities in different individuals and even in different strains of the same experimental animal species. Although there is ample evidence that diverse responses to benzene are related to differences in benzene metabolism, we have recently provided evidence implicating differences in host target cell susceptibility to these diverse responses to benzene. The present study extends our previous work and concerns strain-specific differences in marrow progenitor cells that survive benzene exposure. Two mouse strains (Swiss-Webster and C57B1/6J) which respond to benzene exposure with different intensities of bone marrow cytotoxicity were used. Bone marrow cells from benzene-exposed and untreated mice were cultured with one of five benzene metabolites: 1,4-benzoquinone (BQ), catechol (C), hydroquinone (HQ), muconic acid (MA) or phenol (P) and the abilities of these cells to produce erythroid (CFU-e) or granulocyte/macrophage colonies (GM-CFU-c) were assessed. In both strains, marrow cells isolated from benzene-exposed mice showed a higher percentage of plated CFU-e surviving culture with BQ, HQ or MA than marrow cells isolated from control mice. In contrast, both strains of benzene-exposed mice displayed decreased percentages of plated CFU-e surviving culture with catechol than cells isolated from control mice. Only one condition (the culturing of cells with HQ under GM-CFU-c forming conditions) showed any strain-specific difference in plating efficiency. In all, 20 possible combinations of benzene metabolites and cell types were examined (5 metabolites x 2 progenitor cell types x 2 strains).(ABSTRACT TRUNCATED AT 250 WORDS)
Neun
D J
DJ
Nelson Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Penn
A
A
Snyder
C A
CA
D000818:Animals; D001554:Benzene / Q000494:pharmacology*; D016227:Benzoquinones / Q000633:toxicity*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004351:Drug Resistance; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000502:physiology*; D006098:Granulocytes / Q000502:physiology; D006873:Hydroquinones / Q000633:toxicity*; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism
D016227:Benzoquinones; D006873:Hydroquinones; D013438:Sulfhydryl Compounds; C004532:quinone; D001554:Benzene; C031927:hydroquinone