Conclusions of the French Food Safety Agency on the toxicity of bisphenol A.

Since more than 10 years, risk assessment of bisphenol A (BPA) is debated at the international level. In 2008, the U.S.

Mass spectrometric investigation of the sequence selectivity for adduction of heterocyclic aromatic amines on single-strand oligonucleotides.

Heterocyclic aromatic amines (HAAs) generated during the cooking of meats are known to be genotoxic substances able to form covalent bonds with DNA bases after metabolic activation. This work aimed at the investigation of the influence of the local environment of nucleobases along the nucleotidic sequence on its modification induced by two different HAAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), in order to identify possible sequences more susceptible to modification. A systematic study of the neighbouring base effect on the adduction was emphasized.

New insights in the formation of deoxynucleoside adducts with the heterocyclic aromatic amines PhIP and IQ by means of ion trap MSn and accurate mass measurement of fragment ions.

The formation of adducts by reaction of active metabolites of two heterocyclic aromatic amines (NHOH-PhIP and NHOH-IQ) at nucleophilic sites of deoxynucleosides has been studied by LC-MS(n) analyses of the obtained reaction mixtures. Sequential MS(3) experiments were carried out on an ion trap mass spectrometer to gain extensive structural information on each adduct detected in the first MS step. Attribution of ions was supported by accurate mass measurements performed on an Orbitrap mass analyzer.

Analysis of hemoglobin adducts of acrylamide and glycidamide by liquid chromatography-electrospray ionization tandem mass spectrometry, as exposure biomarkers in French population.

The determination of biomarkers of acrylamide exposure in humans from general French population by measurement of hemoglobin adduct levels of acrylamide (AA) and glycidamide (GA) is presented. The analytical procedure included modified Edman degradation and LC-ESI-MS/MS analysis of the final derivatives using deuterated internal standards. Method performances were evaluated in terms of linearity, precision, accuracy, and sensitivity.

Characterisation of glucosinolates using electrospray ion trap and electrospray quadrupole time-of-flight mass spectrometry.

Twelve naturally occurring glucosinolates displaying alkenyl, hydroxylated, methylsulphinyl, aromatic and indole side chains were investigated by both negative and positive ion electrospray ionisation-tandem mass spectrometry (ESI-MS/MS). In order to resolve the MS/MS spectra obtained from the anion and cation molecular ions of glucosinolates, the different fragments were investigated by MSn experiments using an ion trap spectrometer. The MS3 spectra obtained permitted possible fragmentation schemes to be proposed.

Fumonisin B1 exposure and its selective effect on porcine jejunal segment: sphingolipids, glycolipids and trans-epithelial passage disturbance.

Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium verticillioides, the cause of Fusarium kernel rot in maize. FB(1) is toxic in domestic and laboratory animals, including pigs. This study investigated the effects of a seven-days-exposure of 1.

Assessment of metastable atom bombardment (MAB) ionization mass spectrometry for the fast determination of heterocyclic aromatic amines in cooked meat.

An investigation of metastable atom bombardment (MAB) ionization mass spectrometry for the fast characterization of mutagenic/carcinogenic heterocyclic aromatic amines (HAAs) formed during heating processes of meats is presented. The aim of our study was to use the selective ionization of MAB to develop a detection method for HAAs in non-purified meat extracts, thus avoiding purification and concentration steps and reducing analysis time. Sample introduction into the MAB ion source was achieved by pyrolysis, allowing the direct and fast insertion of complex food extracts into the mass spectrometer.

Mechanism of sulforaphane-induced cell cycle arrest and apoptosis in human colon cancer cells.

Sulforaphane (SFN) is a natural micronutrient found in cruciferous vegetables that has been shown to possess antitumoral properties in carcinogen-treated rats. In vitro, SFN regulates phase II enzymes, cell cycle, and apoptosis. In the present study, we investigated the relationship between SFN induction of apoptosis and cell cycle arrest in HT29 human colon carcinoma cells.

[Carbon monoxide poisoning. Neurologic aspects].

It is most often during winter months that carbon monoxide intoxications occur. Poorly functioning heating systems are the leading cause. We hereby summarize the mechanisms of CO toxicity which leads to treatment basis, and immediate neurological signs of this intoxication.

Isolation and structure elucidation of a new thermal breakdown product of glucobrassicin, the parent indole glucosinolate.

The thermal breakdown of glucobrassicin, the major natural indole glucosinolate present in cruciferous vegetables, has been studied. This study has been conducted using pure synthetic glucobrassicin instead of raw vegetable material to eliminate possible other sources (i.e.

[Diagnosis of internal carotid artery dissection. Two case reports].

Two cases of acute internal carotid dissection are presented. Typical symptoms, pathogeny and imaging features are reviewed. Magnetic Resonance is actually the best technique for the diagnosis of internal carotid artery dissection, which should be searched in young patients presenting neurologic and cervico-facial symptoms.

Purification and characterization of a glutathione S-transferase Omega in pig: evidence for two distinct organ-specific transcripts.

A cytosolic glutathione S-transferase (GST, EC 2.5.1.

Genotoxicity testing of extracts from aflatoxin-contaminated peanut meal, following chemical decontamination.

One of the most important concerns in the decontamination of aflatoxin-containing feed commodities is the safety of the products for food-producing animals and for human consumption of products derived from these animals. A new method, based on the use of florisil and C18 solid phase extraction columns, was developed for the preparation of extracts from decontaminated peanut meal, which allowed testing with in vitro genotoxicity assays without interference of the residual aflatoxin B1. Recovery of degradation products in the extracts was evaluated by the use of radiolabelled [14C]-aflatoxin B1 (AFB1) added to naturally-contaminated peanut meal (3.

Absorption, distribution and excretion of aflatoxin-derived ammoniation products in lactating cows.

Peanut meal naturally contaminated with 3.5 mg/kg aflatoxin B1 (AFB1) was spiked with radiolabelled AFB1 (meal 14C-I0) and decontaminated by a small-scale copy of an industrial ammoniation process (meal 14C-I1). During the process 15% of the radioactivity was lost, whereas 90% of the remaining radiolabel could not be extracted from the meal.

Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells.

Sulforaphane is an isothiocyanate that is present naturally in widely consumed vegetables and has a particularly high concentration in broccoli. This compound has been shown to block the formation of tumors initiated by chemicals in the rat. Although sulforaphane has been proposed to modulate the metabolism of carcinogens, its mechanism of action remains poorly understood.

Flavonoids and the inhibition of PKC and PI 3-kinase.

Flavonoids provide a large number of interesting natural compounds that are consumed daily and exhibit more or less potent and selective effects on some signaling enzymes as well as on the growth and proliferation of certain malignant cells in vitro. Among the identified signal transducers, phosphoinositide 3-kinase (PI 3-kinase) and protein kinase C (PKC) are now considered key players in many cellular responses including cell multiplication, apoptosis, and transformation. Despite their lack of strict specificity, some flavonoids provide valuable bases for the design of analogues that could be used to specifically block particular isoforms of PI 3-kinase or PKC and their downstream-dependent cellular responses.

Metabolism of clenbuterol in rats.

The metabolic fate of [14C]clenbuterol was studied in male and female Wistar rats. After a single oral dose of 200 microgram/kg [14C]clenbuterol, in an 8-day study period, approximately 60% of the radioactivity was eliminated in urine; 20 and 30% of the radioactivity was excreted in feces by male and female rats, respectively. HPLC coupled to on-line radioactivity detection allowed the separation and quantitation of clenbuterol metabolites, some of which were found to be poorly stable in urine.

Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro.

Glucosinolates hydrolysis products are attracting increasing attention since many studies have suggested that they may be involved in the anticarcinogenic property of cruciferous vegetables. In this study, we show that diindolylmethane (DIM) and sulforaphane, produced during the hydrolysis of glucobrassicin and glucoraphanin, respectively, exert a dose-dependent cytotoxicity on human colon adenocarcinoma HT29 cells. Moreover, these products are able to inhibit quiescent cells to re-enter the cell cycle.

Comparative metabolism of clenbuterol by rat and bovine liver microsomes and slices.

The metabolism of clenbuterol by liver microsomal fractions and precision-cut liver slices was studied in rats and cattle using a 14C-labeled molecule and radio-HPLC quantitation of the resulting metabolites. 4-N-Oxidation of clenbuterol was found to be an extensive in vitro metabolic pathway in both species. Clenbuterol hydroxylamine was by far the major metabolite characterized from microsomal and slice incubation media.

Evidence for a new and major metabolic pathway clenbuterol involving in vivo formation of an N-hydroxyarylamine.

Clenbuterol is a beta-adrenergic agonist widely but illegally used in cattle as a growth promoter. The metabolic fate of this drug remains unknown in the main target species, i.e.

Characterization of pig liver glutathione S-transferases using HPLC-electrospray-ionization mass spectrometry.

We have characterized 11 porcine liver cytosolic glutathione S-transferase (GST) subunits from their precise molecular mass, immunoreactivity and partial amino acid sequence. Four Alpha-, six Mu- and one unexpected Pi-class GST subunits were found with average molecular masses of 24.984-25.

Optimization of the separation of beta-agonists by capillary electrophoresis on untreated and C18 bonded silica capillaries.

The conditions of the separation of ten beta-agonists by capillary zone electrophoresis were studied. Several buffers were tested at different ionic strengths and different pH values. The experiments were carried out on two different supports, i.

Electrospray ionization-mass spectrometry as a tool for characterization of glutathione S-transferase isozymes.

Reversed-phase high-performance liquid chromatography coupled to electrospray ionization-mass spectrometry (ESI-MS) was used for the first time to determine the molecular masses of nine rat liver cytosolic glutathione S-transferase (GST) subunits. The precision of the measurements was +/- 3-4 mass units which, in practice, allowed discrimination between monomers differing by more than 8 Da. Mass accuracy was improved by replicates in the measurements.