Abstract：
:Mouse liver tumors that harbor activating mutations in Ctnnb1, encoding β-catenin, express high levels of various cytochromes P450 (CYP), including CYP2E1 and CYP1A2. Acetaminophen (AAP) is metabolized in hepatocytes by these CYPs to the reactive intermediate N-acetyl-p-benzoquinone-imine, which is toxic to hepatocytes at high doses where depletion of glutathione occurs. We have induced liver tumors in mice by treatment with the liver carcinogen N-nitrosodiethylamine followed by chronic treatment with the tumor promoter phenobarbital. Under this protocol, ~80 % of tumors display Ctnnb1 mutations and express high levels of various CYP isoforms. Tumor-bearing animals were given a single intraperitoneal injection of 300 mg/kg body weight AAP, which was well tolerated by the animals. This dose, however, eradicated essentially all larger Ctnnb1-mutated, CYP-positive liver tumors, killing >90 % of hepatoma cells: at 2 days after AAP, large necrotic areas filled with cell debris were observed in tumors. These were infiltrated in the following days by immune cells starting from the outer parts of the damaged areas slowly closing the "wounds" left from the poisoned tumor cells. During this period, there was increased proliferation of normal hepatocytes, but some residual tumor cells were also proliferating. Our results show that a selective poisoning of Ctnnb1-mutated liver tumors by administration of AAP is possible in this experimental system. Application of an adapted protocol could be envisaged for neo-adjuvant treatment of human hepatoblastoma which are frequently mutated in CTNNB1 and often show high expression of CYP2E1.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Singh Y,Braeuning A,Schmid A,Pichler BJ,Schwarz Mdoi
10.1007/s00204-013-1030-8subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1595-607issue
8eissn
0340-5761issn
1432-0738journal_volume
87pub_type
杂志文章abstract：:Changes in the electrophysiologic activity of the rat sciatic nerve were examined after repeated dosing with either of two organophosphate insecticides, parathion, and trichlorfon. Although the parathion treated animals showed overt signs of systemic toxicity, there were no significant changes in any of the measured p...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00333896
更新日期：1983-03-01 00:00:00
abstract：:Several studies have explored the negative effects of cigarette smoke on bone healing; however, the complex pathogenesis still remains unclear. One crucial and primary factor determining effective fracture repair is the recruitment and differentiation of mesenchymal stem cells (MSCs) into bone-forming cells. Recently,...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-017-2149-9
更新日期：2018-04-01 00:00:00
abstract：:Aliphatic nitriles are a class of chemicals used in high volumes in the production of plastics and elastomers, in organic synthesis, and in production of a number of food packaging containers. Toxicity and metabolism of acrylonitrile (AN) are well characterized. On the other hand, minimal information is available on t...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF03208340
更新日期：1994-01-01 00:00:00
abstract：:The toxicity of 60 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) given IP in corn oil/5% acetone was examined in male Sprague-Dawley rats adapted to 25 degrees C or 4 degrees C ambient temperature. Cold exposure significantly reduced mean time to death and tended to increase mortality. Body weight at the ti...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00290540
更新日期：1986-12-01 00:00:00
abstract：:Metabolism of isobutene (2-methylpropene) in rats (Sprague Dawley) and mice (B6C3F1) follows kinetics according to Michaelis-Menten. The maximal metabolic elimination rates are 340 mumol/kg/h for rats and 560 mumol/kg/h for mice. The atmospheric concentration at which Vmax/2 is reached is 1200 ppm for rats and 1800 pp...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02034934
更新日期：1991-01-01 00:00:00
abstract：:N-methylformamide (NMF) produced dose-dependent zone 3 haemorrhagic necrosis in mice; the threshold dose was 100-200 mg/kg. In rats a dose of 1000 mg/kg caused hepatic damage in some animals and slight elevations of plasma transaminases. A species difference in susceptibility to NMF-induced hepatotoxicity is clearly i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00570135
更新日期：1988-01-01 00:00:00
abstract：:Inhabitants of a private home suffered from symptoms possibly due to dichloroacetylene intoxication. Subsequent anamnesis revealed that abundant amounts of trichloroethylene had been used to remove a wax coating from a concrete-lined stone floor. This prompted us to examine whether dichloroacetylene could have been fo...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00349074
更新日期：1984-12-01 00:00:00
abstract：:In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050555
更新日期：1998-10-01 00:00:00
abstract：:Doppler and M-mode echocardiography (EC) were used to investigate the effects of minoxidil on the cardiac function of the dog and potentially to clarify the pathogenesis of cardiac lesions, in particular the necrotic lesion in the left ventricle and the haemorrhagic lesion in the right atrium. Groups of three dogs wer...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0503-6
更新日期：2004-01-01 00:00:00
abstract：:Male F344/DuCrj (Fischer) rats were given bisphenol A (BPA) in the diet at levels of 0 (control), 0.25, 0.50 and 1.00%, equivalent to 0, 235, 466 and 950 mg/kg per day, respectively, for 44 days. Body weight gains were depressed dose-dependently in BPA-treated rats, and those of 0.50 and 1.00% groups were significant....
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040000204
更新日期：2001-03-01 00:00:00
abstract：:Insulin-exposed rat mammary cancer cells were flow sorted based on a c-myc reporter plasmid encoding a destabilized green fluorescent protein. Sorted cells exhibited gradual increases in c-myc levels. Cells overexpressing c-myc by only 10% exhibited phenotypic changes attributable to c-myc overexpression, such as cell...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-009-0463-6
更新日期：2009-12-01 00:00:00
abstract：:Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the org...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02547-x
更新日期：2019-10-01 00:00:00
abstract：:Due to its unique physical structure and chemical properties, graphene family nanomaterials (GFNs) and derived commodities have been widely used in commercial products, particularly biomedical applications, which has significantly increased the risk of human exposure. There exists significant evidence that GFNs are ac...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-020-02717-2
更新日期：2020-06-01 00:00:00
abstract：:The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and pr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1443-z
更新日期：2016-02-01 00:00:00
abstract：:Exposure to alkylanilines found in tobacco smoke and indoor air is associated with risk of bladder cancer. Genetic factors significantly influence the metabolism of arylamine carcinogens and the toxicological outcomes that result from exposure. We utilized nucleotide excision repair (NER)-deficient immortalized human ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-020-02901-4
更新日期：2021-01-01 00:00:00
abstract：:The object of this study was to compare the relative sensitivity of markers of exposure and effects in the lung of rats exposed to polymeric diphenyl-methane-4,4'-diisocyanate (pMDI) aerosol. Rats were repeatedly exposed to 12.9 mg pMDI/m(3) (6 h/day, 5 days/week for 14 days; exposure was from days 0--17 followed by a...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-001-0301-y
更新日期：2002-02-01 00:00:00
abstract：:In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for radiation-induced germ cell mutations was linear and that there was "no escape from the conclusion that there is no threshold". However, assessment of correspondence between Muller and Curt Stern 1 month prior to his N...
journal_title：Archives of toxicology
pub_type： 历史文章,杂志文章
doi：10.1007/s00204-011-0728-8
更新日期：2011-12-01 00:00:00
abstract：:Microsomal and soluble epoxide hydrolase (mEH and sEH) fulfill apparently distinct roles: Whereas mEH detoxifies xenobiotics, sEH hydrolyzes fatty acid (FA) signaling molecules and is thus implicated in a variety of physiological functions. These epoxy FAs comprise epoxyeicosatrienoic acids (EETs) and epoxy-octadeceno...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-017-2060-4
更新日期：2017-11-01 00:00:00
abstract：:Regarding the cancer risk assessment of acrylamide (AA) it is of basic interest to know, as to what amount of the absorbed AA is metabolized to glycidamide (GA) in humans, compared to what has been observed in laboratory animals. GA is suspected of being the ultimate carcinogenic metabolite of AA. From experiments wit...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-008-0296-8
更新日期：2008-10-01 00:00:00
abstract：:Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and S...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-017-2106-7
更新日期：2018-02-01 00:00:00
abstract：:Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta-oxidation and cytochrome P450IVA1 activities. The latter induction of cytochro...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02034935
更新日期：1991-01-01 00:00:00
abstract：:Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and function of hPCLS to 5 d...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1865-x
更新日期：2017-05-01 00:00:00
abstract：:Fifteen patients who were severely poisoned with either hypnotic drugs or salicylate were treated by charcoal haemoperfusion. The device contained 100g of activated charcoal immobilised by fixation to a polyester film. Two patients showed no response and eventually died. The remainder showed marked lightening of coma ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01270911
更新日期：1980-07-01 00:00:00
abstract：:The mycotoxins altertoxin I and II (ATX I and II) are secondary metabolites produced by Alternaria alternata fungi and may occur as food and feed contaminants, especially after long storage periods. Although the toxic potential of altertoxins has been previously investigated, little is known about the pathways that pl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1726-7
更新日期：2017-01-01 00:00:00
abstract：:The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1421-5
更新日期：2015-01-01 00:00:00
abstract：:Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxicity and prevention. Metabolism and ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0109-x
更新日期：2006-12-01 00:00:00
abstract：:Using human neuroblastoma SH-SY5Y cells, effects of acrylamide on p53 protein and intracellular signal transducting pathways were examined. Acrylamide increased p53, phosphorylated p53, and p53-associated protein murine double minute 2 (MDM2). The phosphorylation of p53 was specific for the Ser15 site. Among mitogen-a...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-005-0022-8
更新日期：2006-03-01 00:00:00
abstract：:N-Methyl-2-pyrrolidone (NMP) is a versatile organic solvent frequently used for surface cleaning such as paint stripping or graffiti removal. Liquid NMP is rapidly absorbed through the skin but dermal vapour phase absorption might also play an important role for the uptake of the solvent. This particular aspect was in...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-007-0230-5
更新日期：2008-01-01 00:00:00
abstract：:Diet is directly related with physiological alterations occurring at a cell and subcellular level. However, the role of diet manipulation on mitochondrial physiology is still largely unexplored. Aiming at correlating diet with alterations of mitochondrial membrane composition and bioenergetics, Wistar-Han male rats we...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1068-7
更新日期：2013-12-01 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
