Abstract：
:Checkpoint kinase 1 (Chk1) is required for both intra-S phase and G2/M checkpoints in cell cycle, and plays critical roles in maintaining genomic stability and transducing DNA damage response. Chk1 deficiency has been shown to inhibit T-cell differentiation and resulted in severe anemia in a Chk1 heterozygous mouse model. To date, there has been a good correlation between Chk1 inhibition and in vitro bone marrow toxicity among small molecule inhibitors. To better understand the role of Chk1 in hematopoiesis, we conducted transient Chk1 gene silencing in human bone marrow progenitor cells using siRNA and electroporation. At 48h post electroporation, approximately 70% inhibition of Chk1 was confirmed using real-time RT-PCR and immunoblotting, which resulted in more than 60% reduction in cell count when compared to the non-specific siRNA control on day 6 post-electroporation. This result was confirmed using a colony forming unit assay, where reduced number in both erythroid and granulocyte colonies was observed with Chk1 siRNA treatment. The Chk1 gene inhibition in bone marrow progenitor cells resulted in significant induction of apoptosis, but not cell cycle arrest, as assessed using flow cytometry. In this study an effective method to knock down a gene of interest was established in hard-to-transfect hematopoietic stem cells. Furthermore, our results support a direct role of Chk1 in maintaining normal hematopoiesis in the bone marrow.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Hu W,Zong Q,John-Baptiste A,Jessen Bdoi
10.1016/j.toxlet.2011.04.025subject
Has Abstractpub_date
2011-07-28 00:00:00pages
141-7issue
2-3eissn
0378-4274issn
1879-3169pii
S0378-4274(11)00191-3journal_volume
204pub_type
杂志文章abstract：:The data obtained from in vitro systems utilizing human cells and tissues should form a basic part of the information necessary for risk assessment. The most important thing for such systems is, therefore, to simulate the structures and functions of cells and tissues in the native organ as closely as possible. In desi...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03721-6
更新日期：1996-11-01 00:00:00
abstract：:This paper is a review of epidemiological studies in which sensitive markers of nephrotoxicity have been used to detect the early effects of chemicals on the kidney. Most of the studies are cross-sectional, and their objective was either to identify potentially nephrotoxic chemicals (organic solvents, heavy metals) in...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(89)90137-9
更新日期：1989-03-01 00:00:00
abstract：:A teratological test was carried out on triphenyltin acetate (TPTA) used as a fungicide and antifouling agent. Pregnant Wistar rats were treated orally with TPTA at dose levels of 0, 1.5, 3.0, 6.0, 9.0 and 12.0 mg/kg/d during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. In the pregn...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90108-i
更新日期：1991-04-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and often carcinogenic contaminants released into the environment during natural and anthropogenic combustion processes. Benzo[a]pyrene (B[a]P) is the prototypical carcinogenic PAH, and dibenzo[def,p]chrysene (DBC) is a less prevalent, but highly potent transplace...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.04.004
更新日期：2014-07-03 00:00:00
abstract：:The separation and determination of 3-nitropropionic acid (NPA) in bovine urine by reverse-phase HPLC is described. The method utilizes a rapid ethyl acetate extraction and this clean-up step also improves the chromatographic resolution of NPA in bovine plasma. A simple colorimetric method is also developed for the ra...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90013-c
更新日期：1990-02-01 00:00:00
abstract：:The fast growing applications of ZnO nanoparticles (NPs) in food sector and other fields enhance the exposure possibility of human beings to ZnO NPs including via oral administration route. Although the oral toxicity of ZnO NPs has been studied, most of the research was performed on the normal animal models. Therefore...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.05.038
更新日期：2018-10-01 00:00:00
abstract：:Oral doses of the new cephalosporin cefepime administered to rats for 14 days (40 mg/kg/day) did not affect the activities of the hepatic drug metabolising enzymes measured. By contrast there were highly statistically significant increases in all measured parameters in rats treated with phenobarbitone (80 mg/kg/day), ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)90199-6
更新日期：1994-03-01 00:00:00
abstract：:Phosgene Oxime (CX, Cl2CNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with vesicating agents, is an urticant or nettle agent with highly volatile, reactive, corrosive, and irritating vapor, and has considerably different chemical pr...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2017.11.011
更新日期：2018-09-01 00:00:00
abstract：:Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. We examined whether variations in genes involved in base-excision (hOGG1, XRCC1) and double strand break (XRCC3) DNA repair contribute to inter-individual differences in genotoxic effects induced in ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.12.002
更新日期：2005-04-10 00:00:00
abstract：:N-(3,5-Dichlorophenyl)succinimide (NDPS) induces nephrotoxicity via one or more metabolites which arise from oxidation of the succinimide ring. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3-NDHSA), a potential metabolite of NDPS and a positiona...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(89)90047-7
更新日期：1989-09-01 00:00:00
abstract：:Lindane administration to rats (60 mg/kg b.w.) led to an enhancement in the oxidative stress status of the liver at 4 h after treatment, characterized by increases in hepatic thiobarbituric acid reactants (TBARS) formation and chemiluminescence, reduced glutathione (GSH) depletion, and diminution in the biliary conten...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(00)00172-7
更新日期：2000-04-10 00:00:00
abstract：:An in vivo micronucleus assay using Balb/C male mice was used to examine antigenotoxic effects of cimetidine (CM) on benzene (BZN) induced genotoxic effects. CM not only has therapeutic and immunomudolatory role, but it has also been shown to protect bone marrow stem cells from radiation induced clastogenic effects. T...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00138-6
更新日期：1998-09-30 00:00:00
abstract：:Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.10.010
更新日期：2016-02-26 00:00:00
abstract：:Inhalation of ultrafine particulate matter (PM) in air pollution increases cardiovascular mortality by passing into systemic circulation and possibly affecting endothelial cell (EC) function. This study identified the chemical constituents, including polycyclic aromatic hydrocarbons (PAHs), in diesel exhaust particula...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2007.08.014
更新日期：2007-11-01 00:00:00
abstract：:L-Carnitine is a critical metabolite indispensable for the metabolism of lipids as it facilitates fatty acid transport into the mitochondrion where β-oxidation occurs. Human astrocytes (CCF-STTG1 cells) and hepatocytes (HepG2 cells) exposed to aluminum (Al) and hydrogen peroxide (H₂O₂), were characterized with lower l...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.03.019
更新日期：2011-06-24 00:00:00
abstract：:Little information is available upon the effects of carbon nanotubes (CNT) on the airway barrier. Here we study the barrier function of Calu-3 human airway epithelial cells, grown on permeable filters, after the exposure to commercial single-walled or multi-walled CNT, produced through chemical vapour deposition. To a...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.02.007
更新日期：2008-05-05 00:00:00
abstract：:Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in th...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90226-c
更新日期：1990-03-01 00:00:00
abstract：:Hexachlorobenzene (HCB) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) kinetics were compared in rats before, during and after partial starvation. Food restriction produced a drastic mobilization of the residues stored in the adipose tissue resulting in symptoms of neurotoxicity. The redistribution was reversibl...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90105-1
更新日期：1988-07-01 00:00:00
abstract：:The distribution and acute lethality of i.v. administered 3 micrometers latex spheres were determined in rats. The results extend previous studies demonstrating the similarity between dog and rat in the dynamics of microspheres in these species and the inverse relationship between sphere diameter and hemodynamic toxic...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90035-7
更新日期：1981-10-01 00:00:00
abstract：:288 BALB/c male mice were allocated to: Group 1-control; Group 2-500 ppm of 2-acetylaminofluorene (2-AAF) in the food, with control water; Group 4-500 ppm of 2-AAF in the food and 250 mg/100 ml of vitamin C in the water; and Group 3-control food and 250 mg% of vitamin C in the water. Major histopathologic changes at t...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90136-8
更新日期：1980-09-01 00:00:00
abstract：:Human steroid sulfatase (STS) plays an important role in regulating the formation of biologically active estrogens and may be a promising target for treating estrogen-mediated carcinogenesis. The molecular mechanism of STS gene expression, however, is still not clear. Growth factors are known to increase STS activity ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.09.006
更新日期：2013-11-25 00:00:00
abstract：:It is well known that the oral administration of di-2-ethylhexyl phthalate (DEHP) produces severe seminiferous tubular atrophy in rats, but mice are far less sensitive. In the present experiment, we demonstrated that one strain of mice derived from ICR mice, Crj:CD-1, was very sensitive to DEHP-induced testicular inju...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(93)90078-c
更新日期：1993-01-01 00:00:00
abstract：:Voltage-activated sodium channels and GABAA receptor-chloride channel complex are among the most important target sites of various environmental neurotoxicants. Pyrethroids keep the sodium channels open for prolonged periods of time leading to hyperexcitation of the entire nervous system. In rat cerebellar Purkinje ne...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03482-x
更新日期：1995-12-01 00:00:00
abstract：:To understand environmental causes of disease, unbiased methods are needed to characterize the human exposome, which represents all toxicants to which people are exposed from both exogenous and endogenous sources. Because they directly modify DNA and important proteins, reactive electrophiles are probably the most imp...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.04.002
更新日期：2012-08-13 00:00:00
abstract：:In the olfactory epithelium the primary olfactory neurons are in contact with the environment in the nasal cavity and they are also connected to the olfactory bulbs of the brain. These neurons may therefore provide a pathway by which foreign materials may reach the brain. Inhalation of cobalt-containing dust or fumes ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(03)00266-2
更新日期：2003-11-01 00:00:00
abstract：:Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expres...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.10.024
更新日期：2006-06-01 00:00:00
abstract：:The phthalates di(2-ethylhexyl)phthalate (DEHP) and di-n-butyl phthalate (DBP) are environmental contaminants with significant human exposures. Both compounds are known reproductive toxins in rodents and DEHP also induces rodent hepatocarcinogenesis in a process believed to be mediated via the peroxisome proliferator-...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.11.001
更新日期：2006-06-01 00:00:00
abstract：:Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, acc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.10.006
更新日期：2012-12-17 00:00:00
abstract：:Manganese (Mn) is an indispensable cofactor for many enzymes and a basic factor for many reproductive and metabolic pathways. However, exposure to high concentrations of Mn can result in deleterious effects on the central nervous system and peripheral nerves, including nerves associated with the auditory system. Based...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.07.903
更新日期：2017-09-05 00:00:00
abstract：:Recent hypothesis suggesting a role for environmental toxins in the pathogenesis of neurodegenerative disorders has stimulated interest in research on xenobiotic metabolizing capability of the brain. In addition to possible irreversible loss of neurons through bioactivation in situ in the nervous tissue, the metabolis...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03508-7
更新日期：1995-12-01 00:00:00
