Abstract：
:Some chemicals are known to induce limb malformations in mice. The occurrence of limb abnormality induced by chemical reagents is due to changes in the programmed cell death (PCD). 5-Bromodeoxyuridine (BrdU) is known as a potent teratogen and has been reported to induce polydactyly and other limb malformations in rodents (DiPaolo, Science 145, 501-503, 1964). Here, we undertook the morphological and genetic analyses of fetuses with limb malformations in BrdU-treated mice, in order to investigate an alteration of gene expression that resembles that of mutant mice with similar limb malformations. The fetuses of the BrdU-treated mice exhibited preaxial polydactyly and preaxial triphalangism of the hindlimb at a high incidence. Our observations showed that the PCD in the preaxial necrotic zone was found to be delayed or absent on day 11 of pregnancy. Histological analyses of these fetuses showed that the preaxial apical ectodermal ridge (AER) of the hindlimb was hyperplastic and consisted of several irregular layers. In observation of the whole-mount in situ hybridization, we detected the anterior-extended overexpression of Hoxd-11 and Hoxd-13 genes in the mesenchyme cells and the overexpression of Fgf4 and Fgf8 genes in the anterior region of the AER of hindlimbs of BrdU-treated fetuses. Our study shows that the injection of BrdU changed the PCD and gene expression during limb development and induced time-specific limb malformations during fetal development. This examination of the changes of the PCD and gene expression will be useful markers for the investigation of toxicities and teratologieties of other chemicals now present in the world environment.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Nakamura N,Fujioka M,Mori Cdoi
10.1006/taap.2000.8989subject
Has Abstractpub_date
2000-09-01 00:00:00pages
100-6issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(00)98989-0journal_volume
167pub_type
杂志文章abstract：:This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2nM [(3)H]2, 3, 7, 8-tetr...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.04.015
更新日期：2011-07-01 00:00:00
abstract：:Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible "magic bullet" for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1997.8247
更新日期：1997-11-01 00:00:00
abstract：:In order to visualize the distribution of HI-6 in the rat after iv administration, autoradiographic experiments were carried out with [14C]HI-6, labeled at the carbon of the carboxamide moiety. Autoradiography clearly confirms penetration of HI-6 into the central nervous system. Considerable radioactivity was found in...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90392-4
更新日期：1988-02-01 00:00:00
abstract：:Male, English smooth haired guinea pigs were exposed to thermal decomposition products, i.e., smoke, generated by heating Douglas fir in an open system. Various amounts of Douglas fir were placed in a furnace, at room temperature, and heated at a rate of 11 degrees C/min until completely decomposed. Major decompositio...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90077-2
更新日期：1984-08-01 00:00:00
abstract：:Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the ne...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2015.12.012
更新日期：2016-01-15 00:00:00
abstract：:We report that intracellular calcium levels rise in mammalian neurosecretory terminals and in cultured pheochromocytoma cells during acute exposure to physiological medium incubated in IV drip chambers. The agent responsible for this effect is shown to be di(2-ethylhexyl)phthalate (DEHP). DEHP (800 nM) added to saline...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.9036
更新日期：2000-11-01 00:00:00
abstract：:The elevation of intracellular Ca2+ in various tissue through oxidative stress induced by menadione has been well documented. Increase of Ca2+ level in platelets results in aggregation of platelets. To test the hypothesis that menadione-induced Ca2+ elevations can play a role in platelet aggregation, we have studied t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0092
更新日期：1996-05-01 00:00:00
abstract：:The effect of two concentrations of dietary acid (sulfuric acid) or aluminum (aluminum sulfate) on growth and growth-related hormones was examined in a heavy (broiler) strain of chicken between 4 and 18 days old. Growth (body weight, average daily gain, and tibial length) in chicks receiving either dietary acid or alu...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1137
更新日期：1995-07-01 00:00:00
abstract：:We examined interactions in rats between NO2 gas and respirable aerosols of sulfuric acid (H2SO4) or sodium chloride (NaCl). Rats were exposed for 1, 3, or 7 days to 5 ppm of NO2 gas, alone or in combination with 1 mg/m3 of H2SO4 or NaCl aerosols. The apparent rate of collagen synthesis by lung minces was measured aft...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90303-6
更新日期：1987-08-01 00:00:00
abstract：:Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K(+) channel and Ca(2+) channel blocker effects on QT interval. However, there is no report showing that this techni...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.04.007
更新日期：2014-07-01 00:00:00
abstract：:The 2009 Toxicology and Risk Assessment Conference (TRAC) session on "Advances in Exposure and Toxicity Assessment of Particulate Matter" was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2010.10.020
更新日期：2011-07-15 00:00:00
abstract：:The cDNA sequences for two dioxin-inducible cytochrome P450s in chicken, CYP1A4 and CYP1A5, have recently been reported which correspond to two dioxin-inducible forms of P450 previously designated as TCDDAHH and TCDDAA, respectively. The developmental expression of CYP1A4-associated aryl hydrocarbon (benzo[a]pyrene) h...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8439
更新日期：1998-07-01 00:00:00
abstract：:The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of developmental exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90060-4
更新日期：1989-01-01 00:00:00
abstract：:Acetaminophen (APAP) administration (600 mg/kg, po) results in proximal tubular necrosis in 18-hr fasted, 3-month-old male CD-1 mice. This study was undertaken to determine if deacetylation of APAP to p-aminophenol (PAP) is a prerequisite to nephrotoxicity in the mouse, as it is in the Fischer rat. Administration of e...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(91)90325-9
更新日期：1991-01-01 00:00:00
abstract：:In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples w...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8585
更新日期：1999-03-01 00:00:00
abstract：:Risk assessments are enhanced when policy and other decision-makers have access to experimental science designed to specifically inform key policy questions. Currently, our scientific understanding and science policy for environmental mixtures are based largely on extrapolating from and combining data in the observabl...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2007.02.010
更新日期：2007-09-01 00:00:00
abstract：:Diurnal patterns of eating, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 11 days after a single oral dose of triethyltin bromide (TET) at 0, 1.5, 3, or 5 mg/kg. The 5 mg/kg group exhibited a time-related drop in food consumption and body weight until 3 of 10 rats were sacrificed...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90342-x
更新日期：1986-09-30 00:00:00
abstract：:This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2004.02.016
更新日期：2005-03-15 00:00:00
abstract：:Recent data suggest that vanadium (V5+) compounds exert protective effects against chemical-induced carcinogenesis, mainly through modifying various xenobiotic metabolizing enzymes. In fact, we have shown that V5+ down-regulates the expression of Cyp1a1 at the transcriptional level through an ATP-dependent mechanism. ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.02.002
更新日期：2009-05-01 00:00:00
abstract：:Calcium channel blockers (CCBs) are important in the management of hypertension and limit restenosis. Although CCB efficacy could derive from decreased blood pressure, other mechanisms independent of CCB activity also can contribute to antiproliferative action. To understand mechanisms of CCB-mediated antiproliferatio...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.04.036
更新日期：2012-08-01 00:00:00
abstract：:Para-quinones such as 1,4-Benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophag...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.08.014
更新日期：2014-10-15 00:00:00
abstract：:In rat hepatocytes and isolated liver mitochondrial fractions, Cyclosporine A (CsA) is often used as a specific inhibitor of mitochondrial Ca(2+) release and as a specific blocker of mitochondrial membrane potential and permeability transition (MPT), which are all processes involved in the inhibition of apoptosis. How...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1999.8887
更新日期：2000-03-15 00:00:00
abstract：:Metabolism of BHT (2,6-di-tert-butyl-4-methylphenol) is requisite for its pneumotoxic activities. Previous evidence using microsomal preparations from livers and lungs of mice indicated that cytochrome P450-catalyzed hydroxylation of a tertbutyl group to form 6-tert-butyl-2-(hydroxy-tert-butyl)-4-methylphenol (BHTOH) ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1219
更新日期：1993-11-01 00:00:00
abstract：:Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90117-8
更新日期：1989-06-01 00:00:00
abstract：:The effects of air pollution on human health are a great concern, particularly in big cities with severe traffic problems such as Bangkok, Thailand. In this study, exposure to genotoxic compounds in ambient air was studied by analysis of particle-associated polycyclic aromatic hydrocarbons (PAHs) and benzene through d...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.11.025
更新日期：2005-08-07 00:00:00
abstract：:Kidney is the primary target organ in chronic cadmium (Cd) toxicity, and oxidative stress plays an important role in this process. The nuclear transcription factor Nrf2 binds to antioxidant response elements (AREs) and regulates genes involved in protecting cells from oxidative damage. Whether kidney cells respond to ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.07.038
更新日期：2009-11-15 00:00:00
abstract：:Freely moving rats were exposed to sarin vapor (34.2+/-0.8 microg/l) for 10 min. Mortality at 24 h was 35% and toxic sings in the surviving rats ranged from sever (prolonged convulsions) through moderate to almost no overt signs. Some of the surviving rats developed delayed, intermittent convulsions. All rats were eva...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.11.006
更新日期：2008-03-01 00:00:00
abstract：:Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissue...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.07.016
更新日期：2009-10-15 00:00:00
abstract：:Nuclear receptors (NRs) are key regulators of human health and constitute a relevant target for medicinal chemistry applications as well as for toxicological risk assessment. Several open databases dedicated to small molecules that modulate NRs exist; however, depending on their final aim (i.e., adverse effect assessm...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.115244
更新日期：2020-11-15 00:00:00
abstract：:The mechanism of liver cell injury induced by an overdose of the analgesic acetaminophen (AAP) remains controversial. Recently, it was hypothesized that a significant number of hepatocytes die by apoptosis. Since caspases have been implicated as critical signal and effector proteases in apoptosis, we investigated thei...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1999.8635
更新日期：1999-05-01 00:00:00
