Sensitivity of CFU-E to exogenous erythropoietin in benzene-treated mice (original) (raw)
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The detection of in vivo hematotoxicity of benzene by in vitro liquid bone marrow cultures
Toxicology and applied pharmacology, 1981
Bone marrow toxicity induced by benzene inhalation was investigated in mice using an in vitro bone marrow culture system and a bioassay for 'leukemia. Donor animals (6-week-old female C57Bl/6J) were exposed to 400 ppm benzene 6 hr/day for either 9 days (5 days/week) or for I I consecutive days. Cell suspensions from long-term bone marrow cultures established from benzene-exposed mice showed a progressive reduction in the number of spleen colony-forming cells (the hematopoietic stem cell) compared to control. Different combinations of adherent cell layers and reinoculated cells showed that cultures containing bone marrow cells from benzene-exposed mice had a lower capacity to maintain stem cell proliferation than normal combinations irrespective of whether benzene-exposed marrow was in the adherent cell layers or reinoculated cells. These results indicate that benzene inhalation produces stem cell injury leading to diminished self-replication and derangement of the adherent marrow population. Bone marrow cultures from benzene-treated mice did not develop detectable transformation in vitro throughout the culture period. Neonatal mice inoculated with cultured cells from benzene-exposed mice have not developed leukemia during an S-month period after inoculation.
Action of benzene metabolites on murine hematopoietic colony-forming cellsin vitro
Toxicology and Applied Pharmacology, 1991
Ill, 128-131. Five benzene metabolites--phenol, catechol, hydroquinone, parabenzoquinone, and trans, trans-muconaldehyde--were tested in vitro in murine hematopoietic cell cultures for erythrocytic (BFU-E and CFU-E) and granulocytic (CFU-C) colony growth. The dose range was 4 X l0 4 to 4 X 10 s M. Of these compounds, phenol showed the lowest toxicity. In general, CFU-E cultures were far more sensitive than CFU-C and BFU-E. The results are discussed in relation to the test system used, the in vivo sensitivity of CFU-E, and the lack of knowledge about in vivo concentrations of these compounds.
Effect of in vivo exposure to benzene on the characteristics of bone marrow adherent cells
Leukemia Research, 1983
The effect of benzene on the adherent cell population, cultured from the bone marrow of exposed mice was investigated in the presence and absence of hydrocortisone. The adherent CFUs from exposed animals did not differ either in numbers or self-replicate ability to those derived from shown exposed animals. Adherent layers from mice exposed to 100 or 400 pp-benzene were devoid of fat cells regardless of the presence or absence of hydrocortisone. Hydrocortisone was shown to influence the proportion of acid phosphatase-positive cells derived from benzene-exposed animals. Those results suggest that benzene exposure may influence the bone marrow stromal cells.
In vitro effects of benzene metabolites on mouse bone marrow stromal cells
Toxicology and Applied Pharmacology, 1984
In Vitro Effects of Benzene Metabolites on Mouse Bone Marrow Stromal Cells. GAIDO, K., AND WIERDA, D. (1984). Toxicol. Appl. Pharmacol. 76,[45][46][47][48][49][50][51][52][53][54][55]. Benzene exposure can result in bone marrow myelotoxicity. We examined the effects of benzene metabolites on bone marrow stromal cells of the hemopoietic microenvironment. Male B6C3Fr mouse bone marrow adherent stromal cells were plated at 4 X lo6 cells per 2 ml of DMEM medium in 35-mm tissue culture dishes. The growing stromal cell cultures were exposed to log 2 doses of five benzene metabolites: hydroquinone, benzoquinone, phenol, catechol, or benzenetriol for 7 days. The dose which caused a 50% decrease in colony formation (TD50) was 2.5 X 10e6 M for hydroquinone, 17.8 X low6 M for benzoquinone, 60 X 10e6 M for benzenetriol, 125 X 10e6 M for catechol, and 190 X 10e6 M for phenol. We next examined the effect of benzene metabolites on the ability of stromal cells to influence granulocyte/monocyte colony growth (G/M-CFU-C) in a coculture system. Adherent stromal cells were plated and incubated for 14 days and then exposed to a benzene metabolite. After 3 days the medium and metabolite were removed and an agar:RPMI layer containing lo6 fresh bone marrow cells was placed over the stromal layer. After incubation for 7 days the cultures were scored for G/M colony formation. Hydroquinone and benzoquinone were most toxic, while catechol and benzenetriol inhibited colony growth only at high doses. These results indicate that injured bone marrow stromal Cells may be a significant faCtOr in benzene-induced hemotoxicity. 0 1984 Academic FRSS. 1~.
A model for the induction of aplastic anemia by subcutaneous administration of benzene in mice
Toxicology, 2001
Long-term exposure to benzene vapors is associated with hematological diseases such as leukemia, lymphoma and aplastic anemia. CD 1 male mice were randomly assigned to six groups: 1B 10 , 1B 15 , 1B 20 , 2B 10 , 2B 15 , and 2B 20. 1B mice were administered 2 ml/kg (1940 mg/kg) subcutaneous injection (in the dorsal region) of benzene 5 days a week, and 2B mice were exposed 3 days a week (Monday, Wednesday and Friday) until a total of 10, 15 and 20 doses were completed. About 48 h after treatment completion, leukocyte, erythrocyte, and bone marrow cells were counted, and spleen histopathology was analyzed. 1B 15 and 1B 20 mice showed lethargy and irritability, 80% body and 42% spleen weight loss (PB0.001), while body and spleen weight loss were less severe in 2B mice (12 and 48%, respectively). After exposure to 20 benzene doses, 1B 20 and 2B 20 mice showed decreased hemoglobin concentrations, and erythrocyte, leukocyte and bone marrow cell counts (37, 34, 80 and 50%, respectively in group 1B 20 ; PB 0.001; and 12, 48, 62 and 62%, respectively in group 2B 20). Thrombocytopenia occurred only in group 2B. Both benzene-treatment schemes caused aplastic anemia, however, the disease was masked by spleen toxicity in group 1B. Scheme 2 allowed mice survival and caused less non-hematological effects. We establish here a reproducible and inexpensive experimental model to induce aplastic anemia in mice by subcutaneous injection of 2 ml/kg benzene, using two short-term treatment schemes.
Interactive inhibition of erythroid 59Fe utilization by benzene metabolites in female mice
Chemico-Biological Interactions, 1990
Using radioiron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that benzene inhibited bone marrow function in female mice. Hydroquinone was marginally effective, but the inhibition occurred only at the highest dose tested (100 mg/kg). The combination of phenol and hydroquinone was more effective in reducing erythrocyte production than either chemical given alone. Catechol given alone was not inhibitory but when phenol was added to catechol, erythropoiesis was suppressed, as observed for the phenol and hydroquinone combination. It appears that benzene toxicity may be the result of cooperative inhibitory effects produced by its metabolites.
Chemico-Biological Interactions, 2010
This overview of the Symposium and its organization includes a historical survey of the scientific literature in which the relationship of benzene exposure to the development of aplastic anemia and other bone marrow diseases, including acute myeloid (myelogenous) leukemia, is described. Previous conferences on the health effects of benzene are summarized. The important role of the revised World Health Organization classification of tumors of the hematopoietic and lymphoid tissues in clarifying the specific diseases related to benzene exposure is emphasized.