Chemical suppression of a subpopulation of primitive hematopoietic progenitor cells: 1,3-butadiene produces a hematopoietic defect similar to steel or white spotted mutations in mice.

Colagiovanni, Dorothy B.; Stillman, Wayne S.; Irons, Richard D.

doi:10.1073/pnas.90.7.2803

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…1 B). The identical suppression of CFU is observed when murine HPC are pretreated with epoxybutene, a metabolite of the prototype murine leukemogen, 1,3-butadiene (13). Murine BM pretreated with epoxybutene is completely unresponsive to the effects of ddC, confirming that ddC targets the same subpopulation of clonogenic cells (Fig.…”

Section: Introductionsupporting

confidence: 56%

“…This subpopulation of HPC is identical to that constitutively missing in mice bearing W or Sl mutations that spontaneously develop TL (13). Mice with mutations at the SI and W locus demonstrate complementary defects for SCF, SI mice are deficient in SCF (14), and W mice lack a functional analogous receptor, C-kit (15,16).…”

Section: Introductionmentioning

confidence: 67%

“…Moreover, ddC pretreatment of bone marrow from W/Wv and Sl/Sld mice does not suppress IL-3 (Fig. 3) or alter GM-CSF response (data not shown), indicating that the subpopulation of cells targeted by ddC is the same subpopulation of primitive hematopoietic cells previously demonstrated to be absent in these genetic models (13).…”

Section: Introductionmentioning

confidence: 84%

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2'3'-Dideoxycytidine-induced thymic lymphoma correlates with species-specific suppression of a subpopulation of primitive hematopoietic progenitor cells in mouse but not rat or human bone marrow.

Irons

Le²,

Som³

et al. 1995

J. Clin. Invest.

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The nucleoside analogue, 2',3'-dideoxycytidine (ddC), is a potent inhibitor of HIV replication, and AIDS patients receiving ddC experience clinical improvement without significant hematologic toxicity. Repeated ddC administration (1,000 mg/kg per day) for 13 wk produces an increased incidence of thymic lymphoma in B6C3F1 mice. Previous studies reveal a common link between chemically induced and genetically associated models of mouse thymic lymphoma that involves a defect in a subpopulation of primitive hematopoietic progenitor cells. This defect is characterized by suppression of a subpopulation of IL-3-responsive cells and ablation of stem cell factor synergy with GM-CSF. The present study was undertaken to ascertain whether ddC produces the same pattern of bone marrow toxicity in mice, and whether this effect is observed in rat and human bone marrow. ddC exposure in vivo and in vitro produced a select suppression of murine CFU identical to that previously described for other models of mouse thymic lymphoma. In contrast, this selective CFU suppression was not observed in rat and human bone marrow or in CD34+ cells. These studies suggest that the mouse may not be a good predictive model for ddC hematotoxicity in humans and that susceptibility to the development of thymic lymphoma may be unique to the mouse. (J. Clin. Invest. 1995. 95:2777-2782

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Section: Introductionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 67%

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2'3'-Dideoxycytidine-induced thymic lymphoma correlates with species-specific suppression of a subpopulation of primitive hematopoietic progenitor cells in mouse but not rat or human bone marrow.

Irons

Le²,

Som³

et al. 1995

J. Clin. Invest.

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“…In vitro exposure to HQ induces a time-and dose-dependent increase in phosphorylation of PU.1, the prevalence of CD34 + expression, and cytokine-dependent clonogenic response in cultured HPC HQ has previously been demonstrated to synergize with rhGM-CSF to induce clonogenic response and colony formation in CD34 + HPC (Irons, 1981;Colagiovanni et al, 1993;Irons and Stillman, 1993, 996a,b). HQ treatment of CD34 + HPC resulted in a pattern of PU.1-DNA binding activity consistent with a dose-dependent enhancement in PU.1 phosphorylation that was optimal at 48 h in culture ( Figure 6).…”

Section: Peripheral Blood Monocytes and Granulocytes Exhibit A Distinmentioning

confidence: 92%

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

Zheng

Kerzic

et al. 2006

Cell Biol Toxicol

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The transcriptional regulatory factor PU.1 is important for the regulation of a diverse group of hematopoietic and myeloid genes. Posttranslational phosphorylation of PU.1 has been demonstrated in the regulation of a variety of promoters in normal cells. In leukemia cells, differing patterns of PU.1 phosphorylation have been described among acute myelogenous leukemia (AML) subtypes. Therefore, we hypothesized that modulation of PU.1-dependent gene expression might be a molecular mediator of alterations in myeloid cell growth and differentiation that have been demonstrated to be early events in benzene-induced leukemogenesis. We found that freshly isolated human CD34(+) hematopoietic progenitor cells (HPC) exhibit multiple PU.1-DNA binding species that represent PU.1 proteins in varying degrees of phosphorylation states as determined by phosphatase treatment in combination with electrophoretic mobility shift assay (EMSA). Maturation of granulocyte and monocyte lineages is also accompanied by distinct changes in PU.1-DNA binding patterns. Experiments reveal that increasing doses of the benzene metabolite, hydroquinone (HQ) induce a time-and dose-dependent alteration in the pattern of PU.1-DNA binding in cultured human CD34(+) cells, corresponding to hyperphosphorylation of the PU.1 protein. HQ-induced alterations in PU.1-DNA binding are concomitant with a sustained immature CD34(+) phenotype and cytokine-dependent enhanced clonogenic activity in cultured human HPC. These results suggest that HQ induces a dysregulation in the external signals modulating PU.1 protein phosphorylation and this dysregulation may be an early event in the generation of benzene-induced AML.

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“…After a 30-31 week exposure to butadiene, a significant decrease in the number of CFU-S was observed (512). Other studies suggest that epoxybutene (an epoxide metabolite of butadiene) adversely affects cytokine-mediated cell differentiation in bone marrow in mice (513).…”

Section: Genetic and Related Cellular Effects Studiesmentioning

confidence: 97%

Aliphatic Hydrocarbons

Carreón¹,

Herrick²

2012

Patty's Toxicology

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Aliphatic hydrocarbons are open‐chain compounds that may be saturated or unsaturated. The saturated compounds, known as paraffin hydrocarbons or alkanes , include methane and its homologs having the empirical formula C n H 2 n +2 . The unsaturated compounds fall into a number of homologous series: ( 1 ) those containing one double bond (ethylene and its homologs) and having the formula C n H 2 n are known as olefins or alkenes ; ( 2 ) those containing one triple bond (acetylene and its homologs) are called acetylenes or alkynes and have the formula C n H 2 n −2 ; ( 3 ) those having two double bonds (allene, 1,3‐butadiene and 1,4‐pentadiene represent three types) are diolefins or alkadienes and also have the formula C n H 2 n −2 ; ( 4 ) those having a large number of double or triple bonds or both double and triple bonds are named in analogous fashion as alkatrienes , alkatetraenes , alkadiynes , alkenynes , and alkadienynes . Aliphatic hydrocarbons are asphyxiants and central nervous system ( CNS ) depressants. Serious toxic effects of aliphatic hydrocarbons include asphyxia and chemical pneumonitis for many paraffins, axonal neuropathy for n ‐hexane, and cancer for 1,3‐butadiene.

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Chemical suppression of a subpopulation of primitive hematopoietic progenitor cells: 1,3-butadiene produces a hematopoietic defect similar to steel or white spotted mutations in mice.

Cited by 11 publications

References 36 publications

2'3'-Dideoxycytidine-induced thymic lymphoma correlates with species-specific suppression of a subpopulation of primitive hematopoietic progenitor cells in mouse but not rat or human bone marrow.

2'3'-Dideoxycytidine-induced thymic lymphoma correlates with species-specific suppression of a subpopulation of primitive hematopoietic progenitor cells in mouse but not rat or human bone marrow.

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

Aliphatic Hydrocarbons

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