Abstract：
:Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because drugs may have different effects in human and rodent cells. Previously, we generated a human IL-3 and GM-CSF transgenic humanized mouse (hu-IL-3/GM Tg), in which human granulocytes effectively differentiated after hematopoietic stem cell transplantation. In this study, we established a novel in vivo preclinical evaluation model for predicting human myelotoxicity of anticancer drugs using these hu-IL-3/GM Tg mice. The myelotoxicity was investigated by kinetic flow cytometry of human or murine granulocytes and by colony-forming unit granulocyte/macrophage (CFU-GM) assays. In both in vivo and in vitro analyses, topotecan was more myelotoxic to human than murine granulocytes. In contrast, oxaliplatin was more myelotoxic to murine granulocytes. The level of myelotoxicity of paclitaxel treatment was comparable between human and mouse cells. These results demonstrate that our humanized mouse model can simultaneously evaluate myelotoxicity against human and mouse cells in vivo, and provides an effective preclinical tool for predicting appropriate doses of anticancer agents for clinical treatment.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Ito R,Nagai D,Igo N,Okuda Y,Sekine K,Ichimura E,Katano I,Mizushima T,Goto M,Ohnishi Y,Ito M,Okamoto Kdoi
10.1016/j.toxlet.2017.09.013subject
Has Abstractpub_date
2017-11-05 00:00:00pages
152-157eissn
0378-4274issn
1879-3169pii
S0378-4274(17)31356-5journal_volume
281pub_type
杂志文章abstract：:In recent years physiologically based pharmacokinetic (PBPK) modeling has found frequent application in risk assessments where PBPK models serve as important adjuncts to studies on modes of action of xenobiotics. In this regard, studies on mode of action provide insight into both the sites/mechanisms of action and the...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(02)00375-2
更新日期：2003-02-18 00:00:00
abstract：:Nickel is a metal widely employed in dental alloys, and due to peculiar properties of certain nickel-based materials, it cannot be substituted with other metals in some applications. The release of nickel ions from dental alloys placed into long-term contact with mouth soft tissues is alarming because of the toxic, im...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2005.05.019
更新日期：2005-12-15 00:00:00
abstract：:Autophagy, which works to remove stress and maintain cellular homeostasis, is usually considered a "pro-survival" signal. Contrarily, apoptosis is programmed "pro-death" machinery. Polychlorinated biphenyls (PCBs) are a group of ubiquitous industrial pollutants. Our previous studies illustrated that a PCB quinone meta...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.02.002
更新日期：2019-05-15 00:00:00
abstract：:In this study we evaluated the rat Leydig cell carcinoma cell line R2C and the human adrenocorticocarcinoma cell line H295R for their suitability as in vitro screening tools for potential interference of xenobiotics with aromatase activity. A 24h exposure to prochloraz (PRO), fadrozole (FAD) and epoxyconazole (EPO) re...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2003.10.002
更新日期：2004-01-15 00:00:00
abstract：:The target cell(s) of theobromine toxicity on rat testes and reproductive toxicity induced by pure theobromine and cocoa extract are evaluated in the present studies. Theobromine (500 mg/kg x 7 days) inhibited body weight gain in treated rats. Decreased cauda epididymal sperm reserve (38%), seminiferous tubule fluid (...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)90159-7
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abstract：:This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in ...
journal_title：Toxicology letters
pub_type： 杂志文章,多中心研究
doi：10.1016/j.toxlet.2013.04.008
更新日期：2013-06-20 00:00:00
abstract：:When pregnant mice were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the average time to eye opening in the offspring was shortened by about a day. How acceleration of eye opening by TCDD occurs remains unknown. To reveal the underlying mechanisms of the accelerated eye opening, pregnant mice were intraperit...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.04.001
更新日期：2010-07-01 00:00:00
abstract：:Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 +/- 15.8 micrograms nitrite/h X kg body wt. was detected between 5-24 h. Cerebral glutathione concentration was below the co...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90281-3
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abstract：:Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.10.031
更新日期：2014-10-15 00:00:00
abstract：:The effects of linolic acid hydroperoxides (product A) and secondary oxidative products of product A (product B), were examined in an in vivo mid-term test for hepatocarcinogens or hepatopromoters in rats. The number of placental type of glutathione S-transferase (GST-P)-positive foci of the liver was significantly re...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90048-2
更新日期：1986-07-01 00:00:00
abstract：:Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneou...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.10.009
更新日期：2011-01-15 00:00:00
abstract：:Sublethal exposure to the organochlorine pesticide, dieldrin, decreased the T-cell immune response in mice. Indeed, a transient inhibition of the mixed lymphocyte reactivity (MLR) was noted at 7 days after intraperitoneal exposure to 0.6 LD50 dieldrin. The present study was undertaken to further investigate the effect...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90003-3
更新日期：1988-04-01 00:00:00
abstract：:Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2007.07.004
更新日期：2007-09-10 00:00:00
abstract：:Lipopolysaccharide (LPS) is widely used as a B-lymphocyte mitogen and is known to depress expression of the cytochrome P450 (P450). However, there have been no studies regarding to the effects of the other mitogens on the expression of P450. This study investigated the effects of mitogens on the constitutive and induc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00351-8
更新日期：1999-01-11 00:00:00
abstract：:The impact of organophosphorus compound (OP) intoxication on the activity of central respiratory circuitry, causing acetylcholinesterase (AChE) inhibition and accumulation of acetylcholine in the respiratory brainstem circuits, is not understood. We investigated the central effect of the OP Crotylsarin (CRS) on respir...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.07.005
更新日期：2011-09-25 00:00:00
abstract：:Harmonisation of risk assessment (RA) is one of the priorities for sound chemical management set by Chapter 19, Agenda 21 of the United Nations Conference on the Environment and Development (UNCED) 1992 Earth Summit. The benefits of harmonisation are self evident and include transportability and consistency of RA outc...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(98)00313-0
更新日期：1998-12-28 00:00:00
abstract：:Chloroform-induced toxicity in rodents depends on oral dose regimen. We evaluated the absorption and tissue dosimetry of chloroform after gavage administration in various vehicles to male Fischer 344 rats and female B6C3F1 mice. Animals received a single dose of chloroform in corn oil, water, or aqueous 2% emulphor at...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(97)00023-4
更新日期：1997-05-16 00:00:00
abstract：:Paraquat poisoning results in damages of multiple organs including liver, kidney and lung, and antioxidants have been proven to have protective effects. As a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was introduced to clinical use recently, its protective effect was studied on acute ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(03)00113-9
更新日期：2003-06-05 00:00:00
abstract：:We have previously shown that rituximab has a significant radiosensitizing effect on Raji cells in vitro. To investigate whether calcium signals participate in rituximab- and radiation-induced cell death in Raji cells, confocal laser scanning microscopy was used to detect kinetic changes in intracellular free calcium ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.12.018
更新日期：2012-03-25 00:00:00
abstract：:Treatment of pregnant C57BL/6N mice with 2,3,7,8-tetrachlorodibenzofuran (TCDF) (0, 250, 500, and 1000 micrograms/kg on gestation day 10 or 0, 10, 30, 50, and 100 micrograms/kg on gestation days 10-13) results in dose-related increases in isolated cleft palates and hydronephrotic kidneys in the offspring. TCDF is tera...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90145-0
更新日期：1984-02-01 00:00:00
abstract：:Regions with heavy industry are in many ways regions of crisis. The health of the population is primarily affected by the different air pollutants. Dust, with all its organic (dioxins and furans) and inorganic (heavy metals) contents, makes up the greatest part of the air-borne pollutants. The influence on health of e...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03731-9
更新日期：1996-11-01 00:00:00
abstract：:Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.03.013
更新日期：2013-06-07 00:00:00
abstract：:Dioxins are persistent environmental contaminants that cause multiple disorders in laboratory animals, including teratogenesis. In mice, the most important teratogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are hydronephrosis and cleft palate. Aryl hydrocarbon receptor (AHR) mediates most of the TCDD-in...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.02.009
更新日期：2004-05-02 00:00:00
abstract：:Effect of 120 days of continuous exposure of three sublethal concentrations (1/2, 1/4 and 1/8 fractions of 96 h LC50) of Basalin on alkaline phosphatase (Alk P), acid phosphatase (Acid P), lactic dehydrogenase (LDH), succinic dehydrogenase (SDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transamina...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90184-4
更新日期：1983-05-01 00:00:00
abstract：:Triptolide (TP) is the main ingredient of Chinese herb Tripterygium wilfordii Hook f. (TWHF). Despite of its multifunction in pharmaceutics, accumulating evidences showed that TP caused obvious hepatotoxicity in clinic. The current study investigated the role of Notch1 signaling in TP-induced hepatotoxicity. Our data ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.10.024
更新日期：2019-01-01 00:00:00
abstract：:The effects of cocaine and murine AIDS on natural killer (NK) cell activity in C57BL/6 mice was studied. Cocaine may play a major role in the development and progression to AIDS in the human population. Chronic intraperitoneal injection of cocaine was shown to cause an increase in NK cell activity over those of saline...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90066-f
更新日期：1991-12-01 00:00:00
abstract：:Toxic and volatile chemicals are widely used in household products and previously used as warfare agents, causing a public health threat worldwide. This study aimed to evaluate the extent of injury and mechanisms of acrolein toxicity in the cornea. Primary human corneal stromal fibroblasts cultures (hCSFs) from human ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2021.01.005
更新日期：2021-01-06 00:00:00
abstract：:Pulmonary fibrosis is a serious adverse effect of radiotherapy for thoracic tumor, which is believed to be a process that is tightly regulated by the phenotype of the developing Th response after radiation. Here, we will investigate whether CpG-oligodeoxynucleotides (ODN) prevent radiation-induced pulmonary fibrosis b...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.04.009
更新日期：2018-08-01 00:00:00
abstract：:The mutagenic potential of fluphenazine hydrochloride was tested on male germ cells of Drosophila melanogaster. The criterion used was sex-linked recessive lethal mutations. Oregon-K males of D. melanogaster, reared on a medium containing 0.01, 0.02 and 0.03 mg/ml of the drug, were screened for sex-linked recessive le...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90050-8
更新日期：1980-12-01 00:00:00
abstract：:Prior research suggests that sex hormones and metabolic changes, such as obesity and hyperglycemia, can alter renal transporter expression in rodents. The purpose of this study was to characterize the expression of kidney efflux transporters and regulatory transcription factors in response to Type I diabetes and pregn...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.04.008
更新日期：2012-06-20 00:00:00
