Evidence for strain-specific differences in benzene toxicity as a function of host target cell susceptibility.
It has long been recognized that benzene exposure produces disparate toxic responses among different species or even among different strains within the same species. There is ample evidence that species- or strain-dependent differences in metabolic activity correlate with the disparate responses to benzene. However, bone marrow cells (the putative targets of benzene toxicity) may also exhibit species- or strain-dependent differences in susceptibility to the toxic effects of benzene. To investigate this hypothesis, two sets of companion experiments were performed. First, two strains of mice, Swiss Webster (SW) and C57B1/6J (C57), were exposed to 300 ppm benzene via inhalation and the effects of the exposures were determined on bone marrow cellularity and the development of bone marrow CFU-e (Colony Forming Unit-erythroid, an early red cell progenitor). Second, bone marrow cells from the same strains were exposed in vitro to five known benzene metabolites (1,4 benzoquinone, catechol, hydroquinone, muconic acid, and phenol) individually and in binary combinations. Benzene exposure, in vivo, reduced bone marrow cellularity and the development of CFU-e in both strains; however, reductions in both these endpoints were more severe in the SW strain. When bone marrow cells from the two strains were exposed in vitro to the five benzene metabolites individually, benzoquinone, hydroquinone, and catechol reduced the numbers of CFU-e in both strains in dose-dependent responses, phenol weakly reduced the numbers of the C57 CFU-e only and in a non-dose-dependent manner, and muconic acid was without effect on cells from either strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Neun
D J
DJ
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Penn
A
A
Snyder
C A
CA
D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D016227:Benzoquinones / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D002396:Catechols / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006873:Hydroquinones / Q000633:toxicity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D016227:Benzoquinones; D002396:Catechols; D006873:Hydroquinones; C004532:quinone; D001554:Benzene; C034221:catechol; C031927:hydroquinone