Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure

Abstract

In previous work, we determined that granulocytic (CFU-GM) and erythroid (CFU-E) progenitor cell populations exhibited disparate responses to short-term benzene exposures. We now report on work investigating possible mechanisms for these observed disparate responses. Mice were exposed to either air or 10 ppm benzene for 6 h/d X 5 d. Immediately after the last exposure, mice were injected, i.v., with either saline or hydroxyurea (HU). The dose of HU was sufficient to kill hematopoietic cells in or near S-phase of the cell cycle and sufficient to synchronize the surviving populations of hematopoietic cells. Three days after benzene exposure, CFU-E numbers had declined to 50% of control values while CFU-GM numbers were equal to control values at this time. The benzene exposures were sufficient to double the percentage of CFU-E in S-phase but produced no such increase among CFU-GM. During 3 days of recovery from benzene exposure and HU treatment, the CFU-E population expanded 30-fold while the CFU-GM population expanded less than 3-fold. Following benzene exposure and HU treatment, both progenitor cells produced elevated numbers of their respective progeny. When CFU-E from benzene-exposed mice were cultured with varying concentrations of erythropoietin (EPO), the response at maximal EPO concentration was 66% of the response by control CFU-E. This strongly suggests that the CFU-E populations from benzene-exposed mice had been depleted of cells in or near S-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzene-Induced Hematotoxicity and Bone Marrow Compensation in B6C3F1 Mice

“…This is in contrast to reports showing 10 ppm benzene induced a decrease in CFU-E counts after 5 days exposure, 6 hr/day, in DBA/2J mice (Dempster and Snyder, 1991) and after 32, 66, and 178 days of exposure, 6 hr/day, in C57BI mice (Baarson et al, 1984). In addition, Baarson et al reported a significant decrease in blood erythrocytes in mice exposed to 10 ppm benzene for 66 and 178 days, whereas in the present study mice exposed to 1 or 10 ppm benzene did not have significant changes in the percentage or number of erythropoietic cell (TER + ) counts, reticulocytes, or erythrocytes.…”

ATSDR evaluation of health effects of benzene and relevance to public health

“…Results of many additional studies of laboratory animals (mainly mice, which are particularly sensitive to benzene hematotoxicity, but also rats and pigs) support findings of benzene-induced effects on bone marrow cellularity (hyper-and/or hypocellularity) and colony-forming stem cells, as well as granulocytic hyperplasia, following repeated acute-, intermediate-, or chronicduration inhalation exposure to benzene vapors at concentrations ranging from 10 to 500 ppm (Baarson and Snyder, 1991;Baarson, et al, 1984;Chertkov, et al, 1992;Corti and Snyder, 1996;Cronkite, et al, 1982Cronkite, et al, , 1985Cronkite, et al, , 1989Dempster and Snyder, 1991;Dow, 1992;Farris, et al, 1993Farris, et al, , 1997bNeun, et al, 1992Neun, et al, , 1994Plappert, et al, 1994a,b;Snyder, et al, 1978aSnyder, et al, , 1980Snyder, et al, , 1982Vacha, et al, 1990). For example, Dempster and Snyder (1991) observed a 50% reduction in CFU-E (erythroid progenitor cells) in bone marrow of DBA/2 mice exposed to 10 ppm benzene for 6 h/ day for 5 days. Farris, et al (1997b) reported benzene-induced decreased numbers of total bone marrow forming cells, progenitor cells, and differentiating hematopoietic cells in mice exposed to benzene vapor concentrations ≥200 ppm, 6 h/ day, 5 days/week for up to 8 weeks.…”

“…For example, Dempster and Snyder (1991) observed a 50% reduction in CFU-E (erythroid progenitor cells) in bone marrow of DBA/2 mice exposed to 10 ppm benzene for 6 h/ day for 5 days. Farris, et al (1997b) reported benzene-induced decreased numbers of total bone marrow forming cells, progenitor cells, and differentiating hematopoietic cells in mice exposed to benzene vapor concentrations ≥200 ppm, 6 h/ day, 5 days/week for up to 8 weeks.…”

PU.1 phosphorylation correlates with hydroquinone-induced alterations in myeloid differentiation and cytokine-dependent clonogenic response in human CD34+ hematopoietic progenitor cells

“…Chronic exposure to benzene in vivo is associated with the dysregulation of myeloid development, and HQ has been demonstrated to produce similar alterations in myeloid differentiation in vitro (Cronkite et al, 1989;Dempster and Snyder, 1991;Irons et al, 1992;Irons andStillman, 1993, 1996b). Because PU.1 is an important regulator of lineage commitment and a master regulator of myeloid differentiation, HQ-induced alterations in the regulation of the activity of this transcription factor may explain previously observed alterations in early myeloid development following exposure to benzene.…”