Butyric acid (BA) induces cytodifferentiation in vitro of a wide variety of neoplastic cells. The potential clinical utility of BA is limited by the apparent difficulty of achieving effective concentrations because of its rapid metabolism and short plasma half-life. In this study we addressed two approaches that may achieve effective concentrations of BA in vivo. One strategy is to use BA deriv...

We investigated whether leukemic cell lines could convert hexamethylene bisacetamide (HMBA) to any of the metabolites previously identified and quantified in the urine and plasma of patients treated with HMBA. After 5-7 days of incubation with 1-2 mM HMBA, HL60 human promyelocytic leukemic cells, L1210 and P388 murine lymphoblastic leukemic cells, and Friend murine erythroleukemia cells contain...

In order to study the mechanism of etoposide (VP-16) resistance in human tumor cells and to assess the role of P-170 glycoprotein in VP-16 accumulation, we have examined the uptake and efflux of VP-16 in both sensitive and multidrug-resistant MCF-7 human breast and HL60 human promyelocytic leukemia cells. The drug-resistant cells, MCF-7/ADR and HL60/ADR, were selected for resistance to adriamyc...

We have developed a method that can detect the DNA-damaging and cytotoxic effects of physiological levels of reactive oxygen species (ROS) and activated human neutrophils. This was achieved using WIL2-NS cells, a human B lymphoblastoid cell line, as target cells and the cytokinesis-block micronucleus (CBMN) assay. With this method, we observed a 4- and a 30-fold increase in the frequency of mic...

Studies of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in a cell-free system showed that the low molecular-weight guanosine triphosphatase (GTPase) Rac was required, and that Rapla may participate in activation of the catalytic complex. Full-length posttranslationally modified Rac2 was active, whereas only the 1-166 truncated form of Rapla was functional in...

We have mapped the DNase I-hypersensitive sites around the epsilon-globin and c-myc genes in two human leukemia cell lines K562 and HL60. In K562 cells in which the epsilon-globin gene is transcribed, six DNase I-hypersensitive sites are found in 6 kilobases (kb) of upstream flanking DNA; in HL60 cells in which the c-myc gene is expressed, two DNase I-hypersensitive sites are observed in 2 kb o...

To illustrate the differences in toxicities between deoxynivalenol (DON) and nivalenol (NIV), cell proliferation, cytokine secretion, and the involvement of heat shock protein 90 (Hsp90) were investigated. Both toxins retarded the proliferation of all four cell lines tested. NIV was more potent than DON in human promyelocytic leukemia cell line HL60, human lymphoblastic leukemia cell line MOLT-...

NB4 is an acute promyelocytic leukemia cell line that has been shown to be inducible to terminal neutrophil maturation with all-trans retinoic acid (ATRA). HL60 cells are differentially inducible with 12-O-tetradecanoylphorbol-13-acetate (TPA) or dimethyl sulfoxide (DMSO) to monocytes or granulocytes, respectively. HL60 cells induced with DMSO undergo defective neutrophil maturation, manifested...

Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4(-/-) fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4(+/+) ce...