Abstract：
:Alternative methods to detect non-genotoxic carcinogens are urgently needed, as this class of carcinogens goes undetected in the current testing strategy for carcinogenicity under REACH. A complicating factor is that non-genotoxic carcinogens act through several distinctive modes of action, which makes prediction of their carcinogenic property difficult. We have recently demonstrated that gene expression profiling in primary mouse hepatocytes is a useful approach to categorize non-genotoxic carcinogens according to their modes of action. In the current study, we improved the methods used for analysis and added mouse embryonic stem cells as a second in vitro test system, because of their features complementary to hepatocytes. Our approach involved an unsupervised analysis based on the 30 most significantly up- and down-regulated genes per chemical. Mouse embryonic stem cells and primary mouse hepatocytes were exposed to a selected set of chemicals and subsequently subjected to gene expression profiling. We focused on non-genotoxic carcinogens, but also included genotoxic carcinogens and non-carcinogens to test the robustness of this approach. Application of the optimized comparison approach resulted in improved categorization of non-genotoxic carcinogens. Mouse embryonic stem cells were a useful addition, especially for genotoxic substances, but also for detection of non-genotoxic carcinogens that went undetected by primary hepatocytes. The approach presented here is an important step forward to categorize chemicals, especially those that are carcinogenic.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Schaap MM,Wackers PF,Zwart EP,Huijskens I,Jonker MJ,Hendriks G,Breit TM,van Steeg H,van de Water B,Luijten Mdoi
10.1007/s00204-014-1368-6subject
Has Abstractpub_date
2015-12-01 00:00:00pages
2413-27issue
12eissn
0340-5761issn
1432-0738pii
10.1007/s00204-014-1368-6journal_volume
89pub_type
杂志文章abstract：:Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1673-3
更新日期：2017-01-01 00:00:00
abstract：:Melanin is a polyanionic pigment that colors, e.g., the hair, skin and eyes. The pigment neuromelanin is closely related to melanin and is mainly produced in specific neurons of the substantia nigra. Certain drugs and chemicals bind to melanin/neuromelanin and are retained in pigment cells for long periods. This speci...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-016-1757-0
更新日期：2016-08-01 00:00:00
abstract：:Sarin, a potent organophosphate cholinesterase inhibitor, induces an array of toxic effects including convulsions. Many antidotal treatments contain anticonvulsants to block seizure activity and the ensuing brain damage. Magnesium sulfate (MGS) is used to suppress eclamptic seizures in pregnant women with hypertension...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-012-0916-1
更新日期：2013-02-01 00:00:00
abstract：:To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the l...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01969922
更新日期：1993-01-01 00:00:00
abstract：:Liver microsomes were prepared from Wistar rat by the Ca2+ aggregation method. Under various conditions, ethyl mercury chloride (EtHgCl) or methyl mercury chloride (MeHgCl) was incubated with the microsomal preparations. After the incubation, the amounts of inorganic Hg and hydroxyl radical (.OH) in the preparations w...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02035129
更新日期：1992-01-01 00:00:00
abstract：:The reliable analytical method for total morphine in hair was established by GC/MS-SIM. The calibration curve for morphine in hair showed linear over 0.5-100 ng/mg hair. Though the limit of detection was 0.1 ng/mg hair with an S/N > 3 of the base ion(m/z 429) for morphine, the limit of confirmation by detection of thr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01981507
更新日期：1992-01-01 00:00:00
abstract：:Age-related macular degeneration (AMD) is a late-onset retinal disease and the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial cells (RPE) is a crucial contributing factor responsible for the onset and progression of AMD. The toxic fluorophore N-retinyl-N-retinylidene et...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02637-w
更新日期：2020-02-01 00:00:00
abstract：:Di-n-butylin dichloride (DBTCl), which is commonly used as heat and light stabilizer for polyvinyl chloride (PVC) plastics, is a teratogen in vivo. In the present study, the toxic effects were investigated of DBTCl on cultured rat embryos during three different stages of organogenesis. Rat embryos explanted on gestati...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050335
更新日期：1996-01-01 00:00:00
abstract：:Cadmium, copper and zinc have been determined in kidney cortex, kidney medulla and liver from 51 cadmium-polluted and 122 nonpolluted autopsied subjects. Liver cadmium and zinc were significantly higher in the cadmium-polluted subjects than in the nonpolluted subjects. Kidney cadmium, copper and zinc were lower in the...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316211
更新日期：1987-04-01 00:00:00
abstract：:The OECD has developed an "enhanced Test Guideline 407" (TG 407) protocol for detecting endocrine effects during the course of a 28-day testing scheme. This protocol has gone through a validation process with (anti)estrogenic and (anti)androgenic compounds and substances that affect the thyroid (thyroxine and propylth...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-004-0644-2
更新日期：2005-07-01 00:00:00
abstract：:We recently presented a modified local lymph node test which made it possible to quickly and reliably differentiate between irritative and allergic skin reactions with extremely simple parameters. The Integrated Model for the Differentiation of Skin Reactions (IMDS) test combines measurement of cell proliferation in d...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050001
更新日期：2000-01-01 00:00:00
abstract：:We studied the incorporation of cocaine (COC), benzoylecgonine (BE) and ecgonine methyl ester (EME) into hair from blood. At first, the time courses of three drugs in rat plasma following i.p. administration of cocaine were investigated over 360 min. AUCs of COC, BE and EME in plasma were 14.2, 60.7 and 53.4 microgram...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02035137
更新日期：1992-01-01 00:00:00
abstract：:Assay conditions in determining total cytochrome P-450 in four laboratories were compared. Although the determination was derived from the original Omura and Sato method in each laboratory, the four standard protocols differed slightly, resulting in considerable differences in the results. Since the cytochrome P-450 c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00324544
更新日期：1987-01-01 00:00:00
abstract：:Phenethyl isothiocyanate is a chemopreventive phytochemical present in cruciferous vegetables where it exists as the glucosinolate gluconasturtiin. It is a mechanism-based inhibitor of both rat and human cytochrome P450 enzymes. The principal objective of the present study was to ascertain whether phenethyl isocyanate...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-010-0522-z
更新日期：2010-10-01 00:00:00
abstract：:Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials. To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives. The effects on cell viability, mitochondrial dehydrogenase, and proteog...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01977402
更新日期：1993-01-01 00:00:00
abstract：:Pregnane X receptor (PXR) is a nuclear receptor that plays a key regulatory role in xenobiotic metabolism in a ligand-dependent manner. Recently, ethanol was reported to be either an inducer or inhibitor of Cytochrome P450 (CYP) 3A expression. According to our recent microarray data, chronic ethanol upregulates the ex...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1268-9
更新日期：2015-04-01 00:00:00
abstract：:pp'DDT (600 mg/kg, orally) produced an increase in the level of free ammonia and a decrease of acetylcholine in the corpus striatum of rats. These effects were maximal 5 h after the administration of pp'DDT. The animals showed tremors after 2 h, mild or moderate convulsions after 3.5 h and severe convulsions 5 h after...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00303292
更新日期：1980-05-01 00:00:00
abstract：:Inhibition mechanism(s) of protein kinase B/Akt1 and its consequences on related cell signaling were investigated in human neuroblastoma SH-SY5Y cells exposed to 4-hydroxy-trans-2-nonenal (4-HNE), one of the most reactive aldehyde by-products of lipid peroxidation. In silico data indicate that 4-HNE interacts with kin...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1260-4
更新日期：2015-02-01 00:00:00
abstract：:Morphological changes in mitochondria are observed early in the course of acetaminophen (AA)-induced hepatotoxicity, and mitochondrial dysfunction has been observed both in vivo and in vitro following exposure to AA. This study examined the early effects of AA exposure in vivo on mitochondrial respiration and evaluate...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050043
更新日期：1994-01-01 00:00:00
abstract：:Nephrotoxicity is a major side effect of cisplatin in chemotherapy. Pathologically, cisplatin nephrotoxicity is characterized by cell injury and death in renal tubules. The research in the past decade has gained significant understanding of the cellular and molecular mechanisms of tubular cell death, revealing a centr...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-014-1239-1
更新日期：2014-06-01 00:00:00
abstract：:Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce selectively the expression of CYP2A5 while expression of other CYPs is decreased. In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole (4Me; ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050511
更新日期：1998-05-01 00:00:00
abstract：:Chronic exposure to propiverine, a frequently prescribed pharmaceutical for treatment of overactive bladder and incontinence, provokes massive protein accumulation in the cytosol and nucleus of renal proximal tubule epithelial cells in rats. Previously, the accumulating protein was identified as D-amino acid oxidase (...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1685-z
更新日期：2017-01-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact inhibition ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0601-0
更新日期：2005-01-01 00:00:00
abstract：:The elevations of blood urea nitrogen and serum creatinine caused by cis-platinum in rats can be prevented by a combination of procedures centered around the administration of sodium N-methyl-N-dithiocarboxyglucamine (NaG), before and very soon after the cis-platinum is administered in hypertonic (4.5%) saline. Elevat...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316327
更新日期：1986-10-01 00:00:00
abstract：:The effect of duration of employment at a North American cadmium smelter on urinary metallothionein (MT), total protein, beta 2-microglobulin (beta 2-MG), glucose, cadmium, copper and zinc of 53 men was studied. The levels of all urinary parameters increased with the duration of employment. Smoking history did not aff...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00295090
更新日期：1987-02-01 00:00:00
abstract：:Renal papillary necrosis (RPN) was induced in Fischer 344 (F344) rats (n = 4) using 2-bromoethanamine hydrobromide (BEA) dosed at 150 mg/kg, and in multimammate desert mice (Mastomys natalensis) at 150 and 250 mg/kg (n = 4 per group). Control rats and Mastomys were dosed with 0.9% saline (n = 4 per group). Urine was c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02733668
更新日期：1995-01-01 00:00:00
abstract：:Mice in experimental delay of implantation were injected intravenously with 75 micrograms.g-1 body weight of lead chloride, corresponding to a dose of lead of about 56 micrograms.g-1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02307315
更新日期：1991-01-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) is known to mediate the cellular response to numerous xenobiotics including dioxin. Surprisingly AHR knockout mice provide evidence for the involvement of the AHR signalling cascade in estrogen regulated physiological functions of the female reproductive system. Several studies alre...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-012-0870-y
更新日期：2012-10-01 00:00:00
abstract：:A recent intervention study demonstrated the occurrence of irilone as second most abundant isoflavone next to daidzein in human plasma after consumption of a red clover-based dietary supplement (RCDS) containing predominately formononetin ≫ biochanin A > irilone (12 % of these isoflavones). To elucidate the relevance ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1114-5
更新日期：2014-02-01 00:00:00
abstract：:Pathological changes induced by cadmium aerosol had features common to the changes evoked by oxidants. Female rats were exposed to fumes of lead, antimony, zinc and cadmium (15-100 nmoles/m3). One hour after termination of exposure, superoxide dismutase (SOD) activity in erythrocytes of the exposed rats lowered by 15-...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00347869
更新日期：1982-03-01 00:00:00
