Short term benzene exposure provides a growth advantage for granulopoietic progenitor cells over erythroid progenitor cells

Abstract

Because chronic benzene exposure is associated with acute myeloblastic leukemia and other myeloproliferative disorders, we sought to determine whether short-term benzene exposure provides a growth advantage for granulopoietic elements over erythropoietic elements. Groups of male DBA/2J mice were exposed to 0, 10, 30, or 100 ppm benzene (6 h/day for 5 days). One day and 5 days after the benzene exposures, the numbers of the two most primitive erythroid progenitor cells (BFU-E and CFU-E) and the numbers of the most primitive granulocytic progenitor cells (GM-CFU-C) were assessed. Additional groups of mice were given hemolytic doses of phenylhydrazine (PHZ) during the 5 days of benzene exposure, while other groups of mice were given PHZ during the 5 days of recovery from benzene exposure. These experiments were designed to determine the effects of benzene exposure on progenitor cell numbers during periods of markedly heightened erythropoiesis. The results demonstrate that short-term benzene exposure does induce a growth advantage for granulocytic cells in both the bone marrow and spleen of exposed mice. Moreover, a benzene-induced shift toward granulopoiesis is observed even in those mice treated with a powerful erythropoietic stimulus. These effects disappear 5 days after cessation of benzene exposure in the bone marrow but persist in the spleen of mice treated with phenylhydrazine.

Induction of granulocytic differentiation in a mouse model by benzene and hydroquinone.

“…These results directly support those previously obtained by Seidel (14), and Dempster and Snyder (15). A more indepth examination of the effects of benzene (and its metabolite HQ) on the induction of granulocytic differentiation in mice ( Figure 2) indicated that benzene was able to stimulate the differentiation of myeloblasts, as measured by an increase in the percent of promyelocytes and intermediate granulocytic progenitors in the bone marrow one day after the last benzene injection (3 days after the initiation of treatment), but had no effect on the number of myeloblasts.…”

“…The results of this study indicated that the granulocyte/macrophage colony-forming unit (GM-CFU) was much less sensitive than the erythroid CFUs at higher doses of benzene. Another study (15) reported that short-term exposure of mice to benzene induced a shift toward granulocytic differentiation, a growth advantage for granulocytic progenitor cells in the bone marrow and spleen, and to a resultant increase in the total number of granulocytes. These results suggest that benzene or HQ is acting on the myeloid stem or progenitor cells.…”

An epidemiologic study of early biologic effects of benzene in Chinese workers.

“…The survival and proliferation of stem and progenitor cells are controlled by multiple growth factors, or cytokines, with overlapping functions that act individually or in combination to regulate hematopoiesis. A series of studies carried out in mice and in human bone marrow cultures have shown that benzene alters cytokine production or response to cytokines in the bone marrow (27)(28)(29)(30)(31)(32)(33)(34)(35). To determine if benzene exposure affects cytokine levels measured in peripheral blood, a more accessible and acceptable tissue source than bone marrow, we evaluated a panel of cytokines in the most heavily exposed workers and a subset of controls.…”

Impact of Benzene Metabolites on Differentiation of Bone Marrow Progenitor Cells

“…Enhanced expression of GM-CSF or IL-3 results in profound myelodysplastic changes (4)(5)(6), and altered clonogenic response to GM-CSF is a frequent early observation in the development of acute myelogenous leukemia (AML) (7,8). Moreover, inhalation exposure of mice to benzene enhances clonogenic response to GM-CSF (9,10), and chronic exposure to high concentrations induces a persistent myeloproliferative disorder (10,11). These specific alterations are most likely due to hydroquinone (HQ), which selectively enhances clonogenic response to GM-CSF in murine bone marrow cells (12,13).…”