Abstract：
:The plastic chemical bisphenol A (BPA) has recently been suspected to be a base structure of endocrine disrupting chemicals, which achieve their adverse effects by interfering with human nuclear receptors. For instance, BPA, bisphenol AF, and tetrabromo- or tetrachloro-BPA (X₄-BPA) have been characterized as binders for ERRγ, ER, and PPARγ, respectively. This ongoing string of findings has led to apprehension that some other BPA derivatives might also perturb important human nuclear receptors. The retinoid-related orphan receptor RORγ has been strongly suspected to be a target of highly hydrophobic chemical substances because of its extreme affinity for lipophilic sterols. In the present study, we tested a series of BPA derivatives for their ability to bind to RORγ, and identified two distinctly potent derivatives having isopropyl or sec-butyl groups at positions adjacent to the BPA-4-hydroxyl group. In particular, di-sec-butyl-BPA has emerged as a considerably potent ligand (IC₅₀)=146 nM). In the reporter gene assay, these compounds suppressed the basal constitutive transcriptional activity originally induced by wild-type RORγ. The present results strongly suggested that RORγ, and perhaps also RORα and RORβ, binds highly hydrophobic and sterically hindered chemical substances, inducing some unspecified physiological and biochemical disruptions.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Nishigori M,Nose T,Shimohigashi Ydoi
10.1016/j.toxlet.2012.05.020subject
Has Abstractpub_date
2012-07-20 00:00:00pages
205-11issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(12)01145-9journal_volume
212pub_type
杂志文章abstract：:Isolated rat hepatocytes incubated aerobically formed measurable amounts of ethane, a parameter for lipid peroxidation. This ethane formation increased several-fold due to carbon tetrachloride (CCl4) depending on its concentration. Cell damage as measured by trypan blue uptake and lactate dehydrogenase release poorly ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90112-0
更新日期：1981-06-01 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：:Methylglyoxal (MG) is a metabolite of glucose. The serum MG level is increased in diabetic patients, and MG is implicated in diabetic complications related to embryonic development injury. We previously reported cytotoxic effects of MG on mouse embryonic stem cells and blastocysts, and a further association with defec...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.01.007
更新日期：2010-04-01 00:00:00
abstract：:A considerable body of research over the past fifteen years establishes that in laboratory animals the Ah (aromatic hydrocarbon) receptor (AhR) mediates most, if not all, toxic effects of halogenated aromatic hydrocarbons such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polyhalogenated bip...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(94)90139-2
更新日期：1994-01-01 00:00:00
abstract：:Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects mig...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2020.06.006
更新日期：2020-10-10 00:00:00
abstract：:In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2006.10.006
更新日期：2006-12-15 00:00:00
abstract：:The acute toxicity of fullerenol-1 was determined using mice pretreated intraperitoneally (i.p.) with polyhydroxylated C60 derivatives. The LD50 value of fullerenol-1 was estimated to be 1.2 g/kg. Pretreatments with 0.5 and 1.0 g/kg fullerenol-1 decreased cytochromes P450 and b5 contents, and NADPH-cytochrome P450 red...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(97)00071-4
更新日期：1997-09-19 00:00:00
abstract：:The oxidation of styrene to styrene oxide and the hydration of this metabolite to styrene glycol was investigated in hepatocytes, 9000 x g supernatant (S9) and the microsomal fraction from rat liver. Similar amounts of free styrene oxide were found in microsomes, hepatocytes and S9. However, on the basis of the format...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90120-6
更新日期：1984-11-01 00:00:00
abstract：:There have been many concerns about the possible adverse effects of thyroid hormone-disrupting chemicals in the environment. Because thyroid hormones are essential for regulating the growth and differentiation of many tissues, disruption of thyroid hormones during the neonatal period of an organism might lead to perma...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.01.005
更新日期：2018-04-01 00:00:00
abstract：:The effects of 3 weeks' or 6 months' inhalation exposure of rats to aromatic white spirit 6 h/day, 5 days/week at 0, 400, or 800 ppm were studied. Synaptosomal neurochemistry was investigated as index of the in situ conditions in the presynaptic nerve terminal. In both studies, the relative and absolute yield of synap...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(95)03325-f
更新日期：1995-10-01 00:00:00
abstract：:The exposure to cuprizone (CPZ) leads to demyelination in the central nervous system in rodents. To examine the developmental effects of CPZ exposure on hippocampal neurogenesis, pregnant rats were treated with 0, 0.1 or 0.4% CPZ in the diet from gestational day 6 to day 21 after delivery. On postnatal day 21, male of...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.01.022
更新日期：2015-05-05 00:00:00
abstract：:Iron is a unique poison because it is not a xenobiotic. It is an essential element and highly reactive. Because of the critical dependence upon iron and its potential to damage tissues, elaborate mechanisms have evolved for its efficient absorption, transport, cellular uptake, storage and conservation. These are incom...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00279-3
更新日期：1998-12-28 00:00:00
abstract：UNLABELLED:The Mre11, Rad50, and Nbs1 (MRN) complex is a DNA double-strand break sensor involved in DNA damage repair. Herein, we explored whether deletion of NAD(P)H:quinone oxidoreductase 1 (NQO1), a cytoprotective gene, affected MRN complex expression in the kidney after cisplatin-induced acute kidney injury (AKI)....
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.12.004
更新日期：2016-01-22 00:00:00
abstract：:The US Environmental Protection Agency (EPA) in 1999 issued draft guidelines on carcinogen risk assessment, which included the use mode of action information in the risk assessment process. We have used the five stages of induction of toxicity as described by Aldridge to illustrate in the case of two drugs, tamoxifen ...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(03)00028-6
更新日期：2003-04-11 00:00:00
abstract：:Di-(2-ethylhexyl)-phthalate (DEHP) is a phthalate ester that binds peroxisome proliferator-activated receptor α (PPARα) to induce proliferation of peroxisomes and regulate the expression of specific target genes. The question of whether the effect of DEHP on female reproductive processes is mediated via PPARα-dependen...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.04.019
更新日期：2014-08-04 00:00:00
abstract：:Traditional gold mining, using metallic mercury (Hg(0)) to form gold amalgam, followed by burning to remove the Hg(0), is widely used in South America, Africa and Asia. The gold is sold to merchants who burn it again to eliminate remaining Hg(0). In Ecuador, 200 gold miners, 37 gold merchants and 72 referents were stu...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.09.006
更新日期：2012-08-13 00:00:00
abstract：:The HER2 pathway plays a pivotal role in cell proliferation and differentiation, while the receptor overexpression caused by amplification of HER2 gene is associated with the growth of several tumors. Previously published clinical trials have demonstrated that antibody-conjugated drugs (ADCs) remarkably improved clini...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.12.027
更新日期：2020-05-15 00:00:00
abstract：:This study was conducted to evaluate whether vitamin C (VC) was associated with total antioxidant status (TAS) in human plasma and to determine the usefulness of VC on TAS in the treatment of patients with paraquat poisoning. VC and TAS were measured in 56 healthy subjects. Then, various concentrations (1-100 mg/dl) o...
journal_title：Toxicology letters
pub_type： 临床试验,杂志文章
doi：10.1016/s0378-4274(01)00431-3
更新日期：2002-01-05 00:00:00
abstract：:The activity of femoral-epiphyseal acid phosphatase, a marker enzyme of bone resorption induced by parathyroid hormone, was increased by a single oral dose of Zn 100 mg/kg to rats. This increase was completely inhibited by calcitonin which has antagonistic effect on the action of parathyroid hormone on bone, thus supp...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90276-x
更新日期：1983-10-01 00:00:00
abstract：:Victims of nerve agents basically require antidotal treatment. There is need for novel antidotes and for therapeutic procedures that are specifically adapted to these patients. To cope with this challenge, in vitro test systems which are easy to handle and allow for conducting long-term studies would be of great benef...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.04.010
更新日期：2011-09-25 00:00:00
abstract：:Mice given single i.v. doses of some radiopharmaceuticals containing stannous chloride as a reducing agent, showed significant inhibition of hepatic azo-reductase and aromatic hydroxylase activity at dose levels which contained as little as 0.2 mg/kg of stannous chloride. Cytochrome P-450 content was also reduced sign...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90105-4
更新日期：1983-09-01 00:00:00
abstract：:Hydrazine (Hz) mutagenicity was observed in a test using Escherichia coli B/r strain, WP2 uvrA and was enhanced by the addition of rat liver microsomal fraction containing a generating system, while the enhanced mutagenicity was diminished by the addition of metyrapone to the microsome-free levels. On the other hand, ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(86)90006-8
更新日期：1986-05-01 00:00:00
abstract：:The relative deposition of inhaled heterodisperse particles of the size of environmental tobacco smoke (ETS, mass median aerodynamic diameter 0.2 micron, geometric standard deviation 1.5) is about the same in the tracheobronchial tree and is lower in the pulmonary region of the rat than in the same regions of humans. ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(87)90093-2
更新日期：1987-01-01 00:00:00
abstract：:Pregnant mice of C57BL/6 and DBA/2 inbred strains were exposed to cigarette smoke during days 1-18 of pregnancy. Both mothers and offspring were killed at the age of 21-22 weeks, and ovaries were studied with respect to the number of primordial follicles and small primary follicles. In additional studies, 7,12-dimethy...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(85)90103-1
更新日期：1985-04-01 00:00:00
abstract：:Acetaminophen is a widely used analgesic, which has exhibited evidence of estrogenic activity in estrogen-receptor positive human breast cancer cells. However, there is limited in vivo experimentation regarding the estrogenicity of acetaminophen. Therefore, the present study examined the in vivo estrogenic potential o...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(01)00352-6
更新日期：2001-05-31 00:00:00
abstract：:1. The oocyte of the African clawed toad (Xenopus laevis) offers a reliable, sensitive and disease resistant system to investigate recombinantly and endogenously expressed Ca2+ signaling G protein-coupled receptors and their intracellular signaling pathways. 2. To study receptor induced Ca2+ release, two-electrode vol...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(98)00201-x
更新日期：1998-11-23 00:00:00
abstract：:The capacity of the trichothecene T-2 toxin to alter resistance to bacterial lipopolysaccharide (LPS) was examined in the mouse. Both LPS-susceptible (C3H/HeN) and LPS-resistant (C3H/HeJ) mouse strains exhibited markedly enhanced mortality when a single oral dose of T-2 toxin (1 mg/kg) was coadministered with a subacu...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90146-4
更新日期：1988-11-01 00:00:00
abstract：:There is potential for oral exposure of humans to styrene (ST) such as from migration of residual levels in polystyrene food containers. After absorption, ST is metabolised to styrene-7,8-oxide (SO), an alkylating epoxide. Hence, a comparison of blood burdens of SO resulting from oral exposures to ST was made with SO ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2016.02.001
更新日期：2016-04-15 00:00:00
abstract：:Spontaneous and mitomycin C-induced sister chromatid exchanges (SCEs) in lymphocytes were analyzed in 24 non-smokers and 24 sex- and age-matched smokers. Mean spontaneous SCE frequency for non-smokers was 9.8 SCEs/cell, and that for smokers was 11.5 SCEs/cell. The difference was statistically significant (P less than ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(85)90210-3
更新日期：1985-06-01 00:00:00
abstract：:Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and depletion of striatal dopamine (DA), leading to a range of motor symptoms, including resting tremor, rigidity, bradykinesia and postural abnormalities. The neurotoxin (MPTP) and its active metabol...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.03.003
更新日期：2013-05-23 00:00:00
