Toxicology Research Today is a free monthly online journal that collates and summarizes the latest research about Toxicology, including details on forensic toxicology, carcinogenicity, assays.

Whole embryo culture: a "New" technique that enabled decades of mechanistic discoveries.

Ellis-Hutchings RG, Carney EW

Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.

Denis New's development of the rodent whole embryo culture (WEC) method in the early 1960s was a groundbreaking achievement that gave embryologists and teratologists an unprecedented degree of access to the developing postimplantation rodent embryo. In the five decades since its development, WEC has enabled detailed investigations into the regulation of normal embryo development as well as a plethora of research on mechanisms of teratogenesis as induced by a wide range of agents. In addition, WEC is one of the few techniques that has been validated for use in teratogenicity screening of drugs and chemicals. In this review, we retrace the steps leading to New's development of WEC, and highlight many examples in which WEC played a crucial role leading to important discoveries in teratological research. The impact of WEC on the field of teratology has been enormous, and it is anticipated that WEC will remain a preferred tool for teratologists and embryologists seeking to interrogate embryo development for many years to come. Birth Defects Res (Part B) 89:304-312, 2010. (c) 2010 Wiley-Liss, Inc.

Published 30 August 2010 in Birth Defects Res B Dev Reprod Toxicol, 89(4): 304-12.
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Articles on Toxicology published 30 August 2010:

Methylated DNA Causes a Physical Block to Replication Forks Independently of Damage Signalling, O(6)-Methylguanine or DNA Single-Strand Breaks and Results in DNA Damage.   J Mol Biol, 402(1): 70-82.

Even though DNA alkylating agents have been used for many decades in the treatment of cancer, it remains unclear what happens when replication forks encounter alkylated DNA. Here, we used the DNA fibre assay to study the impact of alkylating agents on replication fork progression. We found that the alkylator methyl methanesulfonate (MMS) inhibits replication elongation in a manner that is dose dependent and related to the overall alkylation grade. Replication forks seem to be completely blocked ... [Abstract] [Full-text]

Molecular characterization, expression analysis, and role of ALDH3B1 in the cellular protection against oxidative stress.   Free Radic Biol Med.

Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of aldehydes. The human genome contains 19 ALDH genes, mutations in which are the basis of several diseases. The expression, subcellular localization, enzyme kinetics, and role of ALDH3B1 in aldehyde- and oxidant-induced cytotoxicity were investigated. ALDH3B1 was purified from Sf9 cells using chromatographic methods, and enzyme kinetics were determined spectrophotometrically. ALDH3B1 demonstrated high affinity for hexanal ... [Abstract] [Full-text]

Biological response and morphological assessment of individually dispersed multi-wall carbon nanotubes in the lung after intratracheal instillation in rats.   Toxicology.

Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single intratracheal instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60nm and 1.5mum, respectively. Groups of male Sprague-Dawley rats were intratracheally instilled with 0.04, 0.2, or 1mg/kg of the individually dispersed MWCNT suspension. After instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, ... [Abstract] [Full-text]

Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary Islands (Spain).   Toxicon.

Ciguatera fish poisoning (CFP) is endemic in certain tropical and subtropical regions of the world. CFP had not been described on the West Africa Coast until a 2004 outbreak in the Canary Islands. In 2008-2009, two additional outbreaks of ciguatera occurred. Individuals afflicted had consumed lesser amberjack (Seriola rivoliana) captured from nearby waters. Caribbean ciguatoxin-1 (C-CTX-1) was confirmed in fish samples by LC-MS/MS. Ciguatoxic fish in this region may pose a new health risk for ... [Abstract] [Full-text]

A multi-target screening analysis in human plasma using fast liquid chromatography-hybrid tandem mass spectrometry (Part I).   Clin Biochem.

OBJECTIVES: Evaluate a new LC-MS/MS screening method for drugs and drugs of abuse as an alternative to the existing methods used in clinical toxicology laboratories. DESIGN AND METHODS: The work was divided in two parts. The first part was dedicated to the technical development and evaluation of the method for which a set of 97 drugs and relevant metabolites was used to perform a complete investigation of matrix effects and lower limit of identification (LOI). The second part was a comparison ... [Abstract] [Full-text]

Comparison of the pharmacological properties of human and rat histamine H(3)-receptors.   Biochem Pharmacol.

Ligand pharmacology of histamine H(3)-receptors is species-dependent. In previous studies, two amino acids in transmembrane domain 3 (TM III) were shown to play a significant role. In this study, we characterized human and rat histamine H(3)-receptors (hH(3)R and rH(3)R, respectively), co-expressed with mammalian G proteins in Sf9 insect cell membranes. We compared a series of imidazole-containing H(3)R ligands in radioligand binding and steady-state GTPase assays. H(3)Rs similarly coupled to ... [Abstract] [Full-text]

Cyclophosphamide and the Teratology society: an awkward marriage.   Birth Defects Res B Dev Reprod Toxicol, 89(4): 289-99.

Cyclophosphamide (CPA) is a potent and highly effective chemotherapeutic and immunosuppressive agent that has been marketed for about 50 years. Reports of its teratogenicity emerged just after the Teratology Society was established, and from that time forth CPA has been inextricably linked to the Society's goal of understanding and preventing birth defects. CPA teratogenesis was previously reviewed (Mirkes, 1985), and since that time the pathways leading to teratogenesis have become more ... [Abstract] [Full-text]

p53-dependent anticancer effects of leptomycin B on lung adenocarcinoma.   Cancer Chemother Pharmacol.

PURPOSE: Leptomycin B (LMB) and/or its derivatives are considered a novel class of cancer therapeutics through blocking chromosome maintenance region 1, which mediates p53 nuclear export. The objectives of the present study were to first evaluate the cytotoxic effects of LMB on a normal human lung epithelial cell line (BEAS-2B) and three human lung adenocarcinoma cell lines with various p53 status (wild type: A549, mutant: NCI-H522, and null: NCI-H358) and then to identify LMB-induced gene ... [Abstract] [Full-text]

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