BPDE-induced genotoxicity: relationship between DNA adducts, mutagenicity in the in vitro PIG-A assay, and the transcriptional response to DNA damage in TK6 cells.
g A Abstract Benzo[a]pyrene is a known human carcinogen. As underlying mechanism, the induction of stable DNA adducts and mutations have been repeatedly demonstrated. Also, the activation of cellular stress response on the transcriptional level has been described. Nevertheless, the interrelationship between these different events is less well understood, especially at low, for human exposure relevant concentrations. Within the present study, we applied the reactive metabolite benzo[a]pyrene diolepoxide (BPDE) in the nanomolar, non-cytotoxic concentration range in human TK6 cells and quantified the induction and re...
Source: Archives of Toxicology - June 7, 2017 Category: Toxicology Authors: Piberger AL, Krüger CT, Strauch BM, Schneider B, Hartwig A Tags: Arch Toxicol Source Type: research

In-utero exposure to nicotine alters the development of the rabbit cardiac conduction system and provides a potential mechanism for sudden infant death syndrome.
Abstract In-utero exposure to tobacco smoke remains the highest risk factor for sudden infant death syndrome (SIDS). To alleviate the risks, nicotine replacement therapies are often prescribed to women who wish to quit smoking during their pregnancy. Cardiac arrhythmias is considered the final outcome leading to sudden death. Our goal in this study was to determine if exposing rabbit fetus to nicotine altered the cardiac conduction system of newborn kittens in a manner susceptible to cause SIDS. Using neuronal markers and a series of immunohistological and electrophysiological techniques we found that nicotine del...
Source: Archives of Toxicology - June 7, 2017 Category: Toxicology Authors: Ton AT, Biet M, Delabre JF, Morin N, Dumaine R Tags: Arch Toxicol Source Type: research

Highlight report: N-acetyltransferase 2 and urinary bladder cancer risk.
PMID: 28577040 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 2, 2017 Category: Toxicology Authors: Blaszkewicz M Tags: Arch Toxicol Source Type: research

Toxicology of silica nanoparticles: an update.
In conclusion, notwithstanding the multiple studies published in recent years, unambiguous linking of physico-chemical properties of SiNPs types to toxicity, bioavailability, or human health effects is not yet possible. PMID: 28573455 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - June 1, 2017 Category: Toxicology Authors: Murugadoss S, Lison D, Godderis L, Van Den Brule S, Mast J, Brassinne F, Sebaihi N, Hoet PH Tags: Arch Toxicol Source Type: research

Conditional loss of hepatocellular Hedgehog signaling in female mice leads to the persistence of hepatic steroidogenesis, androgenization and infertility.
a M Abstract The Hedgehog signaling pathway is known to be involved in embryogenesis, tissue remodeling, and carcinogenesis. Because of its involvement in carcinogenesis, it seems an interesting target for cancer therapy. Indeed, Sonidegib, an approved inhibitor of the Hedgehog receptor Smoothened (Smo), is highly active against diverse carcinomas, but its use is also reported to be associated with several systemic side effects. Our former work in adult mice demonstrated hepatic Hedgehog signaling to play a key role in the insulin-like growth factor axis and lipid metabolism. The current work using mice with an em...
Source: Archives of Toxicology - May 30, 2017 Category: Toxicology Authors: Rennert C, Eplinius F, Hofmann U, Johänning J, Rolfs F, Schmidt-Heck W, Guthke R, Gebhardt R, Ricken AM, Matz-Soja M Tags: Arch Toxicol Source Type: research

Prenatal nicotine exposure induces HPA axis-hypersensitivity in offspring rats via the intrauterine programming of up-regulation of hippocampal GAD67.
Abstract The intrauterine programming of hypothalamic-pituitary-adrenal (HPA) axis hypersensitivity is associated with chronic adult diseases. Our previous studies demonstrated the HPA-axis hypersensitivity in offspring rats induced by prenatal nicotine exposure. The goal of the present study is to further investigate the intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously administered with 2.0 mg/kg day of nicotine from gestational day (GD) 9-20. A group of the pregnant rats was euthanized at GD20, and the fetal rats were extracted. The remaining rats were left to come to term, ...
Source: Archives of Toxicology - May 29, 2017 Category: Toxicology Authors: He X, Lu J, Dong W, Jiao Z, Zhang C, Yu Y, Zhang Z, Wang H, Xu D Tags: Arch Toxicol Source Type: research

On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity.
Abstract Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The present study reveals evidence on the probable protective effects of melatonin on AlP-induced cardiotoxicity in rats. The study groups included a control (almond oil only), ethanol 5% (solvent), sole melatonin (50 mg/kg), AlP (16.7 mg/kg), and 4 AlP + melatonin groups which r...
Source: Archives of Toxicology - May 27, 2017 Category: Toxicology Authors: Asghari MH, Moloudizargari M, Baeeri M, Baghaei A, Rahimifard M, Solgi R, Jafari A, Aminjan HH, Hassani S, Moghadamnia AA, Ostad SN, Abdollahi M Tags: Arch Toxicol Source Type: research

Why are most phospholipidosis inducers also hERG blockers?
Abstract Recent reports have noted that a number of compounds that block the human Ether-à-go-go related gene (hERG) ion channel also induce phospholipidosis (PLD). To explore a hypothesis explaining why most PLD inducers are also hERG inhibitors, a modeling approach was undertaken with data sets comprised of 4096 compounds assayed for hERG inhibition and 5490 compounds assayed for PLD induction. To eliminate the chemical domain effect, a filtered data set of 567 compounds tested in quantitative high-throughput screening (qHTS) format for both hERG inhibition and PLD induction was constructed. Partial least...
Source: Archives of Toxicology - May 27, 2017 Category: Toxicology Authors: Slavov S, Stoyanova-Slavova I, Li S, Zhao J, Huang R, Xia M, Beger R Tags: Arch Toxicol Source Type: research

Commentary to Merwin SJ, Obis T, Nunez Y, Re DB (2017) Organophosphate neurotoxicity to the voluntary motor system on the trail of environment-caused amyotrophic lateral sclerosis: the known, the misknown, and the unknown. Arch Toxicol [Epub ahead of print]. doi:10.1007/s00204-016-1926-1.
PMID: 28540406 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 24, 2017 Category: Toxicology Authors: Lotti M, Moretto A Tags: Arch Toxicol Source Type: research

Mechanisms of hepatotoxicity associated with the monocyclic β-lactam antibiotic BAL30072.
In conclusion, BAL30072 is toxic for liver mitochondria and inhibits glycolysis at clinically relevant concentrations. Impaired hepatic mitochondrial function and inhibition of glycolysis can explain liver injury observed in human subjects receiving long-term treatment with this compound. PMID: 28536862 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 23, 2017 Category: Toxicology Authors: Paech F, Messner S, Spickermann J, Wind M, Schmitt-Hoffmann AH, Witschi AT, Howell BA, Church RJ, Woodhead J, Engelhardt M, Krähenbühl S, Maurer M Tags: Arch Toxicol Source Type: research

Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research.
Abstract Infant leukaemia (
Source: Archives of Toxicology - May 23, 2017 Category: Toxicology Authors: Pelkonen O, Terron A, Hernandez AF, Menendez P, Bennekou SH, EFSA WG EPI1 and its other members Tags: Arch Toxicol Source Type: research

Rabbit N-acetyltransferase 2 genotyping method to investigate role of acetylation polymorphism on N- and O-acetylation of aromatic and heterocyclic amine carcinogens.
Abstract The rabbit was the initial animal model to investigate the acetylation polymorphism expressed in humans. Use of the rabbit model is compromised by lack of a rapid non-invasive method for determining acetylator phenotype. Slow acetylator phenotype in the rabbit results from deletion of the N-acetyltransferase 2 (NAT2) gene. A relatively quick and non-invasive method for identifying the gene deletion was developed and acetylator phenotypes confirmed by measurement of N- and O-acetyltransferase activities in hepatic cytosols. Rabbit liver cytosols catalyzed the N-acetylation of sulfamethazine (p = ...
Source: Archives of Toxicology - May 23, 2017 Category: Toxicology Authors: Hein DW, Doll MA Tags: Arch Toxicol Source Type: research

Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background.
Abstract The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n = 6) ingested AA via coffee (0.15-0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1...
Source: Archives of Toxicology - May 22, 2017 Category: Toxicology Authors: Goempel K, Tedsen L, Ruenz M, Bakuradze T, Schipp D, Galan J, Eisenbrand G, Richling E Tags: Arch Toxicol Source Type: research

Erratum to: S-(3-Aminobenzanthron-2-yl)cysteine in the globin of rats as a novel type of adduct and possible biomarker of exposure to 3-nitrobenzanthrone, a potent environmental carcinogen.
z J, Dušková Š PMID: 28528476 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 20, 2017 Category: Toxicology Authors: Linhart I, Hanzlíková I, Mráz J, Dušková Š Tags: Arch Toxicol Source Type: research

Human cost burden of exposure to endocrine disrupting chemicals. A critical review.
Abstract Recently published papers have alleged that exposures to endocrine disrupting chemicals (EDCs) are causing substantial disease burdens in the EU and US and are consequently costing society hundreds of billions of dollars annually. To date, these cost estimates have not undergone adequate scientific scrutiny, but nevertheless are being used aggressively in advocacy campaigns in an attempt to fundamentally change how chemicals are tested, evaluated and regulated. Consequently, we critically evaluated the underlying methodology and assumptions employed by the chief architects of the disease burden cost estim...
Source: Archives of Toxicology - May 20, 2017 Category: Toxicology Authors: Bond GG, Dietrich DR Tags: Arch Toxicol Source Type: research

Methylone and MDPV activate autophagy in human dopaminergic SH-SY5Y cells: a new insight into the context of β-keto amphetamines-related neurotoxicity.
Methylone and MDPV activate autophagy in human dopaminergic SH-SY5Y cells: a new insight into the context of β-keto amphetamines-related neurotoxicity. Arch Toxicol. 2017 May 19;: Authors: Valente MJ, Amaral C, Correia-da-Silva G, Duarte JA, Bastos ML, Carvalho F, Guedes de Pinho P, Carvalho M Abstract Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity ha...
Source: Archives of Toxicology - May 19, 2017 Category: Toxicology Authors: Valente MJ, Amaral C, Correia-da-Silva G, Duarte JA, Bastos ML, Carvalho F, Guedes de Pinho P, Carvalho M Tags: Arch Toxicol Source Type: research

Catalytic properties and heat stabilities of novel recombinant human N-acetyltransferase 2 allozymes support existence of genetic heterogeneity within the slow acetylator phenotype.
Abstract Human N-acetyltransferase 2 (NAT2) catalyzes the N-acetylation of numerous aromatic amine drugs such as sulfamethazine (SMZ) and hydrazine drugs such as isoniazid (INH). NAT2 also catalyzes the N-acetylation of aromatic amine carcinogens such as 2-aminofluorene and the O- and N,O-acetylation of aromatic amine and heterocyclic amine metabolites. Genetic polymorphism in NAT2 modifies drug efficacy and toxicity as well as cancer risk. Acetyltransferase catalytic activities and heat stability associated with six novel NAT2 haplotypes (NAT2*6C, NAT2*14C, NAT2*14D, NAT2*14E, NAT2*17, and NAT2*18) were compared ...
Source: Archives of Toxicology - May 18, 2017 Category: Toxicology Authors: Hein DW, Doll MA Tags: Arch Toxicol Source Type: research

Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes.
Abstract Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism of numerous drugs and carcinogens. These genetic polymorphisms modify both drug efficacy and toxicity and cancer risk associated with carcinogen exposure. Previous studies have suggested phenotypic heterogeneity among different NAT2 slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ in samples of human hepatocytes obtained from various NAT2 slow and intermediate NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A) was observed towa...
Source: Archives of Toxicology - May 17, 2017 Category: Toxicology Authors: Doll MA, Hein DW Tags: Arch Toxicol Source Type: research

Environmental toxicants, incidence of degenerative diseases, and therapies from the epigenetic point of view.
Abstract Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary cond...
Source: Archives of Toxicology - May 17, 2017 Category: Toxicology Authors: Hodjat M, Rahmani S, Khan F, Niaz K, Navaei-Nigjeh M, Mohammadi Nejad S, Abdollahi M Tags: Arch Toxicol Source Type: research

Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells.
Abstract The liver is a dynamic organ which is both multifunctional and highly regenerative. A major role of the liver is to process both endo and xenobiotics. Cigarettes are an example of a legal and widely used drug which can cause major health problems for adults and constitute a particular risk to the foetus, if the mother smokes during pregnancy. Cigarette smoke contains a complex mixture of thousands of different xenobiotics, including nicotine and polycyclic aromatic hydrocarbons. These affect foetal development in a sex-specific manner, inducing sex-dependant molecular responses in different organs. To dat...
Source: Archives of Toxicology - May 16, 2017 Category: Toxicology Authors: Lucendo-Villarin B, Filis P, Swortwood MJ, Huestis MA, Meseguer-Ripolles J, Cameron K, Iredale JP, O'Shaughnesy PJ, Fowler PA, Hay DC Tags: Arch Toxicol Source Type: research

Erratum to: Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016.
PMID: 28508230 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - May 15, 2017 Category: Toxicology Authors: Silva MJ, Wong LY, Samandar E, Preau JL, Calafat AM, Ye X Tags: Arch Toxicol Source Type: research

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target.
Abstract The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related halogenated aromatics. Other toxic compounds including some polynuclear aromatic hydrocarbons act through the AhR; however, during the last 25 years, it has become apparent that the AhR plays an essential role in maintaining cellular homeostasis. Moreover, the scope of ligands that bind the AhR includes endogenous compounds such as multiple tryptophan metabolites, other endogenous biochemicals, pharmaceuti...
Source: Archives of Toxicology - May 15, 2017 Category: Toxicology Authors: Kolluri SK, Jin UH, Safe S Tags: Arch Toxicol Source Type: research

MicroRNAs in injury and repair.
Abstract Organ damage and resulting pathologies often involve multiple deregulated pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. Since their discovery over two decades ago, miRNAs have been established as key players in the molecular mechanisms of mammalian biology including the maintenance of normal homeostasis and the regulation of disease pathogenesis. In recent years, there has been substantial progress in innovative techniques to measure miRNAs along with advances in targeted delivery of agents modulating their expression. This ha...
Source: Archives of Toxicology - May 13, 2017 Category: Toxicology Authors: Gerlach CV, Vaidya VS Tags: Arch Toxicol Source Type: research

A primer on systematic reviews in toxicology.
Abstract Systematic reviews, pioneered in the clinical field, provide a transparent, methodologically rigorous and reproducible means of summarizing the available evidence on a precisely framed research question. Having matured to a well-established approach in many research fields, systematic reviews are receiving increasing attention as a potential tool for answering toxicological questions. In the larger framework of evidence-based toxicology, the advantages and obstacles of, as well as the approaches for, adapting and adopting systematic reviews to toxicology are still being explored. To provide the toxicology...
Source: Archives of Toxicology - May 13, 2017 Category: Toxicology Authors: Hoffmann S, de Vries RBM, Stephens ML, Beck NB, Dirven HAAM, Fowle JR, Goodman JE, Hartung T, Kimber I, Lalu MM, Thayer K, Whaley P, Wikoff D, Tsaioun K Tags: Arch Toxicol Source Type: research

Hepatic glucuronidation of 4-tert-octylphenol in humans: inter-individual variability and responsible UDP-glucuronosyltransferase isoforms.
Abstract 4-tert-Octylphenol (4-tOP) is an endocrine-disrupting chemical. It is mainly metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in humans. The purpose of this study was to assess inter-individual variability in and the possible roles of UGT isoforms in hepatic 4-tOP glucuronidation in the humans. 4-tOP glucuronidation activities in the liver microsomes and recombinant UGTs of humans were assessed at broad substrate concentrations, and kinetics were analyzed. Correlation analyses between 4-tOP and diclofenac or 4-hydroxybiphenyl activities in pooled and individual human liver microso...
Source: Archives of Toxicology - May 12, 2017 Category: Toxicology Authors: Isobe T, Ohkawara S, Tanaka-Kagawa T, Jinno H, Hanioka N Tags: Arch Toxicol Source Type: research

Trans-generational neurochemical modulation of methamphetamine in the adult brain of the Wistar rat.
aacute; M, Bubenikova-Valešová V, Beste C, Šlamberová R Abstract Chronic methamphetamine (METH) abuse has been shown to elicit strong neurotoxic effects. Yet, with an increasing number of children born to METH abusing mothers maturing into adulthood, one important question is how far do the neurotoxic effects of METH alter various neurotransmitter systems in the adult METH-exposed offspring. The purpose of this study was to investigate long-term trans-generational neurochemical changes, following prenatal METH exposure, in the adult Wistar rat brain. METH or saline (SAL-control animals)...
Source: Archives of Toxicology - May 5, 2017 Category: Toxicology Authors: Fujáková-Lipski M, Kaping D, Šírová J, Horáček J, Páleníček T, Zach P, Klaschka J, Kačer P, Syslová K, Vrajová M, Bubenikova-Valešová V, Beste C, Šlamberová R Tags: Arch Toxicol Source Type: research

Combination of multiple neural crest migration assays to identify environmental toxicants from a proof-of-concept chemical library.
Abstract Many in vitro tests have been developed to screen for potential neurotoxicity. However, only few cell function-based tests have been used for comparative screening, and thus experience is scarce on how to confirm and evaluate screening hits. We addressed these questions for the neural crest cell migration test (cMINC). After an initial screen, a hit follow-up strategy was devised. A library of 75 compounds plus internal controls (NTP80-list), assembled by the National Toxicology Program of the USA (NTP) was used. It contained some known classes of (developmental) neurotoxic compounds. The primary screen y...
Source: Archives of Toxicology - May 5, 2017 Category: Toxicology Authors: Nyffeler J, Dolde X, Krebs A, Pinto-Gil K, Pastor M, Behl M, Waldmann T, Leist M Tags: Arch Toxicol Source Type: research

Ex vivo human skin permeation of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI).
Abstract Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are biocides used in many types of products such as cosmetics, paints, and cleaning agents. Skin contact is often encountered when using these products. Although MCI and MI are strong allergens and cause skin irritation, no scientific skin permeation study has been reported except for some unpublished data. Therefore, this study assessed the permeation of MCI and MI both separately and as a mixture through freshly dermatomed human skin (800 µm) in a flow-through diffusion cell system. Different concentrations of aqueous standards ...
Source: Archives of Toxicology - May 3, 2017 Category: Toxicology Authors: Berthet A, Spring P, Vernez D, Plateel G, Hopf NB Tags: Arch Toxicol Source Type: research

Arsenic-mediated hyperpigmentation in skin via NF-kappa B/endothelin-1 signaling in an originally developed hairless mouse model.
In this study, hairless homozygous mice (Hr/Hr-mice) that drank water containing 3 and 30 µM arsenic for 2 months developed skin hyperpigmentation with increased levels of arsenic and number of melanocytes in the skin. Since it is possible for humans to be exposed to 3 µM of arsenic in well drinking water, our results suggest that the Hr/Hr-mice could be a novel model sensitively reflecting arsenic-mediated skin hyperpigmentation. We then analyzed the mechanism of arsenic-mediated skin hyperpigmentation. The epidermis of Hr/Hr-mice and human HaCaT skin keratinocytes exposed to arsenic for 2 and 4...
Source: Archives of Toxicology - May 3, 2017 Category: Toxicology Authors: Yajima I, Kumasaka MY, Iida M, Oshino R, Tanihata H, Al Hossain A, Ohgami N, Kato M Tags: Arch Toxicol Source Type: research

In vitro uptake and toxicity studies of metal nanoparticles and metal oxide nanoparticles in human HT29 cells.
Abstract In this paper, we investigated the toxicological behavior of metal nanoparticles (gold, silver) and metal oxide nanoparticles (copper oxide, zinc oxide, titanium dioxide) in vitro in human colorectal adenocarcinoma cells (HT29). We analyzed the cellular uptake by ICP-MS and TEM, the influence on cell viability by MTT assay and trypan blue exclusion test, their effect on DNA damage and/or generation of oxidized bases by alkaline comet assay, and their potential to induce apoptosis by flow cytometry after 24-h nanoparticle treatment with concentrations between 2 and 10 µg/ml. We determined the am...
Source: Archives of Toxicology - May 2, 2017 Category: Toxicology Authors: Schneider T, Westermann M, Glei M Tags: Arch Toxicol Source Type: research

Erratum to: Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines.
PMID: 28451738 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 27, 2017 Category: Toxicology Authors: Hsieh MJ, Tsai TL, Hsieh YS, Wang CJ, Chiou HL Tags: Arch Toxicol Source Type: research

Understanding renal nuclear protein accumulation: an in vitro approach to explain an in vivo phenomenon.
Abstract Proper subcellular trafficking is essential to prevent protein mislocalization and aggregation. Transport of the peroxisomal enzyme D-amino acid oxidase (DAAO) appears dysregulated by specific pharmaceuticals, e.g., the anti-overactive bladder drug propiverine or a norepinephrine/serotonin reuptake inhibitor (NSRI), resulting in massive cytosolic and nuclear accumulations in rat kidney. To assess the underlying molecular mechanism of the latter, we aimed to characterize the nature of peroxisomal and cyto-nuclear shuttling of human and rat DAAO overexpressed in three cell lines using confocal microscopy. I...
Source: Archives of Toxicology - April 27, 2017 Category: Toxicology Authors: Luks L, Maier MY, Sacchi S, Pollegioni L, Dietrich DR Tags: Arch Toxicol Source Type: research

Precision toxicology based on single cell sequencing: an evolving trend in toxicological evaluations and mechanism exploration.
Abstract In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell i...
Source: Archives of Toxicology - April 27, 2017 Category: Toxicology Authors: Zhang B, Huang K, Zhu L, Luo Y, Xu W Tags: Arch Toxicol Source Type: research

On the necessity of translational cognitive-neurotoxicological research in methamphetamine abuse and addiction.
PMID: 28444486 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 25, 2017 Category: Toxicology Authors: Stock AK, Beste C Tags: Arch Toxicol Source Type: research

Tributyltin in male mice disrupts glucose homeostasis as well as recovery after exposure: mechanism analysis.
Abstract Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the a...
Source: Archives of Toxicology - April 10, 2017 Category: Toxicology Authors: Li B, Guo J, Xi Z, Xu J, Zuo Z, Wang C Tags: Arch Toxicol Source Type: research

Lanthanum chloride precipitation-based toxicoproteomic analysis of 3-monochloropropane-1,2-diol toxicity in rat kidney reveals involvement of extracellular signal-regulated kinase 2.
Abstract The heat-induced food contaminant 3-monochloropropane-1,2-diol (3-MCPD) and its fatty acid esters exert nephrotoxicity in rodents. Previous studies including a non-targeted toxicoproteomics approach using samples from a 28-day oral toxicity study in rats with 10 mg/kg body weight (b.w.) of 3-MCPD, an equimolar dose of 53 mg/kg b.w. 3-MCPD dipalmitate and a lower dose of 13.3 mg/kg b.w. of 3-MCPD dipalmitate, revealed substance-induced alterations in metabolic pathways, especially for glycolysis and energy metabolism. In order to obtain deeper insight into mechanisms of 3-MCPD toxicity, samp...
Source: Archives of Toxicology - April 9, 2017 Category: Toxicology Authors: Oberemm A, Braun M, Sawada S, Pink M, Frenzel F, Rozycki C, Meckert C, Zabinsky E, Braeuning A, Lampen A Tags: Arch Toxicol Source Type: research

Rat precision-cut liver slices predict drug-induced cholestatic injury.
In conclusion, our results indicate that PCLS may represent a physiological and valuable model to identify cholestatic drugs and provide insight into the mechanisms underlying DIC. PMID: 28391356 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 8, 2017 Category: Toxicology Authors: Starokozhko V, Greupink R, van de Broek P, Soliman N, Ghimire S, de Graaf IA, Groothuis GM Tags: Arch Toxicol Source Type: research

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated deregulation of myeloid and sebaceous gland stem/progenitor cell homeostasis.
Abstract Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed. (2) Accumulation of TCDD in sebum leads to deregulation of sebocyte d...
Source: Archives of Toxicology - April 6, 2017 Category: Toxicology Authors: Bock KW Tags: Arch Toxicol Source Type: research

Comprehensive analysis of the in vitro and ex ovo hemocompatibility of surface engineered iron oxide nanoparticles for biomedical applications.
Abstract A set of biomedically relevant iron oxide nanoparticles with systematically modified polymer surfaces was investigated regarding their interaction with the first contact partners after systemic administration such as blood cells, blood proteins, and the endothelial blood vessels, to establish structure-activity relationships. All nanoparticles were intensively characterized regarding their physicochemical parameters. Cyto- and hemocompatibility tests showed that (1) the properties of the core material itself were not relevant in short-term incubation studies, and (2) toxicities increased with higher polym...
Source: Archives of Toxicology - April 4, 2017 Category: Toxicology Authors: Schlenk F, Werner S, Rabel M, Jacobs F, Bergemann C, Clement JH, Fischer D Tags: Arch Toxicol Source Type: research

Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin.
This study now shows that readily isolable skin commensals transform B[a]P into a range of highly cyto- and genotoxic metabolites that are excreted in toxicologically relevant concentrations during growth. The respective bacterial supernatants contain a mixture of established eukaryotic as well as hitherto unknown prokaryotic metabolites, the combination of which leads to an increased toxicity. Altogether we show that PAH metabolism of the microbiome has to be considered a potential hazard. PMID: 28378121 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - April 4, 2017 Category: Toxicology Authors: Sowada J, Lemoine L, Schön K, Hutzler C, Luch A, Tralau T Tags: Arch Toxicol Source Type: research

Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells.
Abstract Manganese (Mn) is an essential trace metal which plays a critical role in brain physiology by acting as a cofactor for several enzymes. However, upon overexposure, Mn preferentially accumulates within the basal ganglia leading to the development of a Parkinsonism known as Manganism. Data from our group have proved that Mn induces oxidative stress-mediated apoptosis in astrocytoma C6 cells. In the present study we described how cathepsins impact on different steps of each apoptotic cascade. Evidence obtained demonstrated that Mn generates lysosomal membrane permeabilization (LMP) and cathepsin release. Bot...
Source: Archives of Toxicology - April 4, 2017 Category: Toxicology Authors: Gorojod RM, Alaimo A, Porte Alcon S, Saravia F, Kotler ML Tags: Arch Toxicol Source Type: research

Chalcone flavokawain B induces autophagic-cell death via reactive oxygen species-mediated signaling pathways in human gastric carcinoma and suppresses tumor growth in nude mice.
We examined the in vitro and in vivo anticancer activity and autophagy involvement of FKB and determined the underlying molecular mechanisms. FKB is potently cytotoxic to human gastric cancer cells (AGS/NCI-N87/KATO-III/TSGH9201) and mildly toxic towards normal (Hs738) cells and primary mouse hepatocytes. FKB-induced AGS cell death was characterized by autophagy, not apoptosis, as evidenced by increased LC3-II accumulation, GFP-LC3 puncta and acidic vesicular organelles (AVOs) formation, without resulting procaspase-3/PARP cleavage. FKB further caused p62/SQSTM1 activation, mTOR downregulation, ATG4B inhibition, and Beclin...
Source: Archives of Toxicology - April 3, 2017 Category: Toxicology Authors: Chang CT, Hseu YC, Thiyagarajan V, Lin KY, Way TD, Korivi M, Liao JW, Yang HL Tags: Arch Toxicol Source Type: research

Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC.
Abstract Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. ...
Source: Archives of Toxicology - April 3, 2017 Category: Toxicology Authors: Tarazona JV, Court-Marques D, Tiramani M, Reich H, Pfeil R, Istace F, Crivellente F Tags: Arch Toxicol Source Type: research

Impairment of human neural crest cell migration by prolonged exposure to interferon-beta.
t M Abstract Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the 'migration inhibition of neural crest' (MINC) assay. Concentration-response studies in the MINC combined w...
Source: Archives of Toxicology - April 1, 2017 Category: Toxicology Authors: Pallocca G, Nyffeler J, Dolde X, Grinberg M, Gstraunthaler G, Waldmann T, Rahnenführer J, Sachinidis A, Leist M Tags: Arch Toxicol Source Type: research

The human microbiome, from Achilles armour to Nessus' shirt.
PMID: 28357486 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 29, 2017 Category: Toxicology Authors: Tralau T, Luch A Tags: Arch Toxicol Source Type: research

Lesson of 15-year exposure to Bisphenol A: a critical discussion of biomonitoring studies.
l W PMID: 28357487 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 29, 2017 Category: Toxicology Authors: Völkel W Tags: Arch Toxicol Source Type: research

Study on inter-ethnic human differences in bioactivation and detoxification of estragole using physiologically based kinetic modeling.
Abstract Considering the rapid developments in food safety in the past decade in China, it is of importance to obtain insight into what extent safety and risk assessments of chemicals performed for the Caucasian population apply to the Chinese population. The aim of the present study was to determine physiologically based kinetic (PBK) modeling-based predictions for differences between Chinese and Caucasians in terms of metabolic bioactivation and detoxification of the food-borne genotoxic carcinogen estragole. The PBK models were defined based on kinetic constants for hepatic metabolism derived from in vitro...
Source: Archives of Toxicology - March 29, 2017 Category: Toxicology Authors: Ning J, Louisse J, Spenkelink B, Wesseling S, Rietjens IM Tags: Arch Toxicol Source Type: research

Time-matched analysis of DNA adduct formation and early gene expression as predictive tool for renal carcinogenesis in methylazoxymethanol acetate treated Eker rats.
r K Abstract Genotoxic carcinogens pose great hazard to human health. Uncertainty of current risk assessment strategies and long latency periods between first carcinogen exposure and diagnosis of tumors have raised interest in predictive biomarkers. Initial DNA adduct formation is a necessary step for genotoxin induced carcinogenesis. However, as DNA adducts not always translate into tumorigenesis, their predictive value is limited. Here we hypothesize that the combined analysis of pro-mutagenic DNA adducts along with time-matched gene expression changes could serve as a superior prediction tool for genotoxic carc...
Source: Archives of Toxicology - March 27, 2017 Category: Toxicology Authors: Klaus V, Bastek H, Damme K, Collins LB, Frötschl R, Benda N, Lutter D, Ellinger-Ziegelbauer H, Swenberg JA, Dietrich DR, Stemmer K Tags: Arch Toxicol Source Type: research

Gut microbiome-related metabolic changes in plasma of antibiotic-treated rats.
Abstract The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites. To identify plasma metabolites related to microbiome changes due...
Source: Archives of Toxicology - March 23, 2017 Category: Toxicology Authors: Behr C, Kamp H, Fabian E, Krennrich G, Mellert W, Peter E, Strauss V, Walk T, Rietjens IM, van Ravenzwaay B Tags: Arch Toxicol Source Type: research

Biotransformation of 2,4-toluenediamine in human skin and reconstructed tissues.
In conclusion, our results underline the principal suitability of RHS as an adequate test matrix for the investigation of N-acetylation of xenobiotics which is most relevant for risk assessment associated with cutaneous exposure to aromatic amines. PMID: 28337504 [PubMed - as supplied by publisher] (Source: Archives of Toxicology)
Source: Archives of Toxicology - March 23, 2017 Category: Toxicology Authors: Grohmann L, Becker D, Rademann J, Ma N, Schäfer-Korting M, Weindl G Tags: Arch Toxicol Source Type: research