Abstract：
:Some chemicals are harmful in to light-exposed tissues such as skin and eyes. The 3T3 Neutral Red Uptake Phototoxicity Test has been validated and adopted by the Organization of Economic and Community Development (OECD) as a method of evaluating chemical phototoxicity using mouse 3T3 fibroblasts. However, the high rate of false positive results associated with this test eventually led to increased laboratory animal usage. Although the eye is vulnerable to light damage because of constant exposure to environmental radiation, few approaches are available to predict ocular phototoxicity in humans. Here, we propose a tier one test that identifies the potential ocular phototoxicity of chemical substances. Using a three-dimensional culture technique, human embryonic stem cells (hESCs) were differentiated to retinal pigment epithelial cell (RPE) precursors. The precursors after prolonged treatment with FBS formed a uniform hexagonal lattice of cells with well-developed tight junctions and time-dependent elevation of melanin content and RPE maturation marker levels. Hierarchical clustering of gene transcripts revealed that hESC-derived RPEs were very similar to tissue-derived adult RPEs. Interestingly, there were a high percentage of chemicals eliciting a positive response in 3T3 cells and negative in hESC-derived RPEs under the experimental conditions used in the phototoxicity test. The response to treatment of hESC-derived RPEs with these negative chemicals became positive at a higher dose of UVA irradiation; however, the biological responses to these chemicals differed between the two cells. Taken together, we conclude that hESC-derived RPEs are novel tool for future toxicological and mechanistic studies of ocular phototoxicity in humans.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Mori T,Higashi K,Nakano T,Ando S,Kuwahara A,Suzuki N,Saito Kdoi
10.1016/j.tox.2017.01.003subject
Has Abstractpub_date
2017-03-01 00:00:00pages
1-9eissn
0300-483Xissn
1879-3185pii
S0300-483X(17)30004-5journal_volume
378pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract：:Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2012.04.007
更新日期：2012-08-16 00:00:00
abstract：:Chemicals can increase carcinogenic risk by either directly damaging DNA or increasing cell replication or they can do both. These effects have different implications for a biologically-based extrapolation from rodent bioassays to humans. 2-Acetylaminofluorene (2-AAF) administered at low doses to mice for a lifetime h...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/0300-483x(95)03044-g
更新日期：1995-09-01 00:00:00
abstract：:Heavy metals, such as iron and manganese, are involved in neurologic disease. Most often these diseases are associated with abnormal environmental exposures or abnormal accumulations of heavy metals in the body. There is increasing recognition that heavy metals normally present in the body also may play a role in dise...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/0300-483x(94)02962-t
更新日期：1995-03-31 00:00:00
abstract：:The in vivo toxicity of the novel copper-based anticancer agent, casiopeina II (Cu(4,7-dimethyl-1,10-phenanthroline)(glycine)NO3) (CII), was investigated. Casiopeinas are a family of copper-coordinated complexes that have shown promising anticancer activity. The major toxic effect attributed to a single i.v. administr...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2003.08.009
更新日期：2003-12-15 00:00:00
abstract：:Immunohistochemical methods have been widely used to determine the histogenesis of spontaneous and chemically-induced mouse lung tumors. Typically, antigens for either alveolar Type II cells or bronchiolar epithelial Clara cells are studied. In the present work, the morphological and immunohistochemical phenotype of a...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(03)00060-x
更新日期：2003-05-03 00:00:00
abstract：:Mercury has been a known as a toxic substance for centuries. Whilst the clinical features of acute mercury poisoning have been well described, chronic low dose exposure to mercury remains poorly characterised and its potential role in various chronic disease states remains controversial. Low molecular weight thiols, i...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/j.tox.2007.02.016
更新日期：2007-05-20 00:00:00
abstract：:We have reported that excessive nitric oxide (NO), like other reactive oxygen species (ROS), causes a decrease in cytochrome c oxidase (CCO) activity and ATP levels (mitochondrial damage) resulting in lens opacity. In addition, previous reports have shown that oxidative stress caused by ROS enhances amyloid β (Aβ) pro...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2017.02.014
更新日期：2017-04-15 00:00:00
abstract：:The nitric oxide (NO) donor, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO in the liver and possibly other tissues. V-PYRRO/NO has been shown to be hepatoprotective, but little is known about its effect in the kidney, another organ rich in P450s. Thus...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(03)00129-x
更新日期：2003-08-01 00:00:00
abstract：:This study was undertaken to investigate whether treatment with vitamin E (VE) and/or vitamin C (VC) protects rat sperm by inhibiting reactive oxygen species generation induced by lead (Pb) exposure. Male Sprague-Dawley rats were assigned to the following five groups: vitamin-unsupplemented; 150 mg VE/kg chow suppleme...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(98)00068-7
更新日期：1998-07-17 00:00:00
abstract：:Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. The pathogenesis of DILI usually involves the participation of the parent drug or metabolites that either directly affect the cell biochemistry or elicit an immune response. However, in most cases the mechanisms a...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2010.05.011
更新日期：2010-09-10 00:00:00
abstract：:The synthetic pyrethroid insecticide, cypermethrin, was given during gestation to pregnant rats by gavage in corn oil. Peripheral blood and spleen cytotoxic activity of dams and their offspring were then evaluated at different times (30, 60, 90, 120 days) after birth. Pups showed a significant increase in peripheral b...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(97)03662-7
更新日期：1997-07-11 00:00:00
abstract：:The prevalence of asthma is increasing worldwide. The increase has been found for both sexes, for all races and age groups. The factors responsible are unclear. The short period of increase makes it unlikely that a genetic change is responsible but rather suggests that either air pollutants or a behavioral change may ...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/s0300-483x(02)00298-6
更新日期：2002-12-27 00:00:00
abstract：:A recent epidemiological study showed an increased risk for bone fractures after chronic low-level cadmium exposure. This finding agrees with those of cadmium accumulation in rat bones after chronic oral exposure which reduced the mechanical strength of the bones. There are indications that ossicular cadmium uptake ma...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(00)00364-4
更新日期：2001-02-21 00:00:00
abstract：:The mean concentrations of polybrominated diphenyl ethers (PBDEs) (sum tetra- to octaBDEs) were determined in samples of foodstuffs widely consumed by the population of Catalonia, Northeast Spain. The following six tetra-through heptabrominated congeners were also individually analyzed: PBDEs 47, 99, 100, 153, 154 and...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/j.tox.2008.03.006
更新日期：2008-06-03 00:00:00
abstract：:The Internet = s global reach offers new powerful tools to professionals in Occupational and Environmental Health (OEH). The World Wide Web includes extensive free and commercially available reference materials on toxicology, regulatory issues, environmental epidemiology and prevention programs. Much of this especiall...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/s0300-483x(02)00028-8
更新日期：2002-04-25 00:00:00
abstract：:The attempts to use nitroxide free radicals and nitrone spin traps topically in skin requires analysis of their potential cutaneous adverse effects. The objective of this study was to investigate the skin irritation and sensitizing potential of nitroxides and nitrones in the guinea pig. The following unsubstituted nit...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(97)00183-2
更新日期：1998-02-20 00:00:00
abstract：:We have developed a model for the treatment of data of concentration of brain neurotransmitters (particularly serotonin and the catecholamines), in which the changes induced by any given treatment on the neurotransmitter (NT) and its main metabolite (ME) are converted into 2 new parameters named S and U, that are rela...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(88)90173-4
更新日期：1988-04-01 00:00:00
abstract：:Exposure to polycyclic aromatic hydrocarbons (PAHs) always involves complex mixtures that may induce synergistic or antagonistic effects on the genotoxic properties and make risk assessment more difficult. In this study, we evaluated how particulate PAHs modulated the formation of DNA damage induced by carcinogenic be...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2010.09.002
更新日期：2011-01-11 00:00:00
abstract：:The distribution and excretion of radioactivity from [14C]citrinin (3 mg/kg, i.v) was determined in male rats. At 0.5 h after administration maximum values of 14.7% and 5.6% of total radioactivity were observed in the liver and kidneys, respectively, and by 6 h decreased to 7.5% in the liver and 4.7% in the kidney. Pl...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(79)90075-1
更新日期：1979-03-01 00:00:00
abstract：:The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid synthetase (ALA.S) and delta-aminolaevulinic acid dehydratase (ALA.D) were measured in the peripheral blood of a group of lead workers and control subjects. The haem precursor delta-aminolaevulinic acid (ALA) was measured in blood and urine, whil...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(78)90026-4
更新日期：1978-02-01 00:00:00
abstract：:Chronic ethanol intake affects various organ systems of the body. The present study evaluated modifications of fatty acid concentrations both in brain and striated skeletal muscles of rats genetically selected for voluntary high ethanol intake. Three groups of rats were tracked for 10 weeks of access to ethanol only a...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2004.02.023
更新日期：2004-07-01 00:00:00
abstract：:The usefulness of measuring serum bile acid concentrations by RIA in a number of acute experimental liver injuries of rats was assessed by comparing the concentrations with the results of some of the routinely employed methods of examining hepatotoxic changes. Centrilobular liver cell injury produced by CCl4 revealed ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(80)90005-0
更新日期：1980-01-01 00:00:00
abstract：:Transgenic rat mutation assays can be used to assess genotoxic properties of chemicals in target organs for carcinogenicity. Mutations in transgenes are genetically neutral and accumulate during a treatment period; thus, assays are suitable for assessing the genotoxic risk of chemicals using a repeated-dose treatment ...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2014.07.003
更新日期：2014-10-03 00:00:00
abstract：:The aim of this study was to assess whether microwave-induced DNA damage is basal or it is also generated through reactive oxygen species (ROS) formation. After having irradiated Wistar rats with 915MHz microwave radiation, we assessed different DNA alterations in peripheral leukocytes using standard and formamidopyri...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2009.02.008
更新日期：2009-05-17 00:00:00
abstract：:Induction of hepatic metallothionein (MT) by acetaminophen was characterized in the rat and mouse. Treatment of rats with the hepatotoxin resulted in increase of liver MT in a dose-dependent manner. MT concentration was elevated by 41%, 140% and 260% following acetaminophen injection at doses of 250, 500 and 1000 mg/k...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(88)90224-7
更新日期：1988-12-30 00:00:00
abstract：:Indoor suspended particulate matter (SPM) consists of many different types of particles, the vast majority of which are less than 2.5 microm in diameter. An important question is how these particles, being inhalable, contribute to asthma and respiratory symptoms. One possibility is that these particles have an adjuvan...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/s0300-483x(98)00079-1
更新日期：1998-08-21 00:00:00
abstract：:Cadmium being a potent immunotoxicant, affects both humoral and cell mediated immunity. However, its effect on spleen is not clearly understood. Hence, to delineate the action of Cd, mouse splenic lymphocytes were exposed to Cd (10, 25 and 50 microM) for 60 min, 1.5, 3, 6 and 18 h. At 6 h, apoptosis was reflected by D...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/j.tox.2005.11.027
更新日期：2006-03-01 00:00:00
abstract：:Malthion, DDT, kelthane and their mixture (3 : 10 : 5) were applied to pear fruits at the rate recommended by the Ministry of Agriculture. The rate of disappearance of their residues on pear fruits was investigated under refrigerated conditions (2 +/- 1 degree and 47% relative humidity (RH)). The same insecticides wer...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(75)90094-3
更新日期：1975-05-01 00:00:00
abstract：:The importance of dietary factors for prostate carcinogenesis has been proven by epidemiological studies of immigrants from Asia into the USA. Intake of foodstuffs rich in fat, including meat, is suggested to be a risk factor. Experimentally, while some studies demonstrated high fat intake to promote rat prostate carc...
journal_title：Toxicology
pub_type： 杂志文章,评审
doi：10.1016/s0300-483x(02)00260-3
更新日期：2002-12-27 00:00:00
abstract：:Cultures of the human cell line NHIK 3025 were exposed over an 18-month period to 0.5 mumol/1 potassium dichromate (K2Cr2O7) containing 1 mumol/1 hexavalent chromium. The chronically exposed cells increased their tolerance to K2Cr2O7 in comparison to control populations. The doubling time of the chronically exposed ce...
journal_title：Toxicology
pub_type： 杂志文章
doi：10.1016/0300-483x(81)90083-4
更新日期：1981-01-01 00:00:00
