Comparison of PGC and Biphenyl stationary phases for the high throughput analysis of DNA epigenetic modifications by UHPLC-MS/MS.

Epigenetic alterations such as cytosine methylation, hydroxymethylation, formylation and carboxylation are well known modifications that are frequently associated with various disease such as cancer. These modifications are usually studied at the gene level to evaluate their impact on the expression of genes but there is a need for a whole genome quantification that can be more easily used as effect biomarkers. Here, we compare two high throughput methods for the UHPLC-MS/MS analysis of these four epigenetic markers in large cohort studies.

Agricultural exposures and DNA damage in PBMC of female farmers measured using the alkaline comet assay.

Objective: Several studies investigated the link between agricultural occupational exposures and DNA damage, in an attempt to bring elements of biological plausibility to the increased cancer risk associated with them. However, only a few of these studies focused on females.

Methods: The comet assay was performed on PBMC (Peripheral Blood Mononuclear Cells) samples from 245 females working in open field farming and cattle raising, located in the Normandy area of France.

UHPLC-MS/MS method for the quantification of ultra-traces of irinotecan and its metabolites in red blood cells and plasma to detect caregivers' contamination.

The occupational exposure of caregivers to antineoplastic agents has been demonstrated since 1979. Since the early 1990s, numerous studies from several countries have demonstrated the contamination of care facilities by antineoplastic drugs. As it is easier to sample, most contamination measurements in workers are carried out in urine sample.

In vitro genotoxicity potential investigation of 7 oxy-PAHs.

Air pollutants include many compounds among them oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs). As they are suspected to generate DNA damage and mutagenicity, an understanding of their mode of action could highlight a carcinogenic potential risk in exposed population. In this article, a prospective study on seven oxy-PAHs selected in terms of occurrence in the environment was conducted on mutagenicity, genotoxicity, and cytotoxicity potentials using in vitro assays including Ames test on five strains, kinetic analysis of cytotoxicity and apoptosis, phosphorylation of histone H2AX, and p53 induction assays on human lung cell line BEAS-2B.

Impact of low- and high-risk operators handling irinotecan on the blood contamination of health care workers in oncology day care units.

Introduction: Health care workers handling antineoplastic drugs (ADs) are at risk of mutagenicity and adverse reproductive effects. Despite protective equipment and AD handling guidelines, AD levels are still detected in caregivers in oncology units. This study attempted to assess blood contamination by irinotecan and its metabolites in all health care workers in oncology day hospital units according to activities specific to each employment category.

Is the blood of a surgeon performing HIPEC contaminated by irinotecan, its major metabolites and platinum compounds?

Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) is a beneficial surgical technique for patients, but the surgeons are being exposed to cytotoxic drugs. Few biomonitoring studies were led on blood samples in the context of HIPEC. This study aimed to evaluate the surgeon's plasmatic and red blood cell (RBC) contamination by irinotecan, two of its major metabolites and platinum compounds.

Blood contamination of the pharmaceutical staff by irinotecan and its two major metabolites inside and outside a compounding unit.

Background: Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit.

Investigation by mass spectrometry and P post-labelling of DNA adducts formation from 1,2-naphthoquinone, an oxydated metabolite of naphthalene.

Naphthalene is the simplest representative of polycyclic aromatic hydrocarbons (PAHs). It is detected as major pollutant in the different compartments of the environment. This compound is considered by the international agency for research on cancer (IARC), the specialized cancer agency of the World Health Organisation (WHO), as a possible carcinogenic (group 2B) since 2002, mainly based on studies on chronic inhalation in rodent by the national toxicology program of the U.

Pyridoclax-loaded nanoemulsion for enhanced anticancer effect on ovarian cancer.

Background: Pyridoclax is an original lead, recently identified as very promising in treatment of chemoresistant ovarian cancers. To correct the unfavorable intrinsic physico-chemical properties of this BCS II drug, a formulation strategy was implied in the drug discovery step. Pyridoclax-loaded nanoemulsions (NEs) were developed to permit its preclinical evaluation.

Does equipment change impact blood contamination with irinotecan and its two major metabolites in a centralized cytotoxic pharmacy unit?

Background: Antineoplastic drugs exposure is a major problem for caregivers' health. The aim of this study is to assess blood contamination with irinotecan and its two metabolites in a centralized pharmacy unit for cytotoxic drug preparations workers before and after protective equipment changes.

Methods: The study took place in a university hospital centralized pharmacy unit for cytotoxic drug and was performed in two parts, before (Round 1: R1) and after equipment changes (Round 2: R2).

A validated UHPLC-MS/MS method for simultaneous quantification of 9 exocyclic DNA adducts induced by 8 aldehydes.

Human exposure to aldehydes is implicated in several diseases including cancer. These strong electrophilic compounds can react with nucleophilic sites in DNA to form reversible and irreversible modifications. These modifications, if not repaired, can contribute to pathogenesis.

The Antitumoral Effect of the S-Adenosylhomocysteine Hydrolase Inhibitor, 3-Deazaneplanocin A, is Independent of EZH2 but is Correlated with EGFR Downregulation in Chondrosarcomas.

Background/aims: 3-Deazaneplanocin, DZNep, has been reported to inhibit the EZH2 histone methylase and to induce cell apoptosis in chondrosarcomas (CS). The present study aims to confirm the therapeutic potential of EZH2 inhibitors and investigate the molecular mechanisms of DZNep in chondrosarcomas.

Methods: CS cell lines and primary cultures were used.

Plasminogen Activator Inhibitor-1 (PAI-1) deficiency predisposes to depression and resistance to treatments.

Major depressive disorder (MDD) is one of the most frequent psychiatric illnesses, leading to reduced quality of life, ability to work and sociability, thus ranking among the major causes of disability and morbidity worldwide. To date, genetic and environmental determinants of MDD remain mostly unknown. Here, we investigated whether and how the Plasminogen Activator Inhibitor-1 (PAI-1) may contribute to MDD.

Oxy-PAHs: occurrence in the environment and potential genotoxic/mutagenic risk assessment for human health.

Structurally modified polycyclic aromatic hydrocarbons (PAHs) such as nitrated PAHs (nitro-PAHs) and oxygenated PAHs (oxy-PAHs) can be incriminated in the total toxicity of polycyclic aromatic compounds (PACs) fraction in the environment. Compared to nitro-PAHs, oxy-PAHs have been poorly studied. Oxy-PAHs covers compounds with different moieties such as polycyclic aromatic ketones (PAKs) and polycyclic aromatic quinones (PAQs).

Is hyperthermic intraperitoneal chemotherapy (HIPEC) safe for healthcare workers?

Background: During hyperthermic intraperitoneal chemotherapy (HIPEC), caregivers are exposed by different routes to cytotoxic drugs. This review proposes an overview of the safety of HIPEC by assessing existing data on protection procedures, biological and non-biological samples. Based on these data, relevant good practices, eventual irrelevant overprotection procedures and missing data to implement adapted protections are highlighted.

Love Acoustic Wave-Based Devices and Molecularly-Imprinted Polymers as Versatile Sensors for Electronic Nose or Tongue for Cancer Monitoring.

Cancer is a leading cause of death worldwide and actual analytical techniques are restrictive in detecting it. Thus, there is still a challenge, as well as a need, for the development of quantitative non-invasive tools for the diagnosis of cancers and the follow-up care of patients. We introduce first the overall interest of electronic nose or tongue for such application of microsensors arrays with data processing in complex media, either gas (e.

Synthesis of a molecularly imprinted polymer to isolate glucosamine from plant extracts by an ionic-non-covalent dual approach.

Objective: The objective of this study was to synthesize a novel glucosamine-imprinted sorbent based on ionic and non-covalent dual approach to purify glucosamine from chicory root extracts.

Methods: The synthesis of the molecularly imprinted polymer was optimized in terms of choice of monomers, porogen, cross-linker and initiator to have the best recognition as possible for targeted molecule. The sorbent obtained was characterized by nitrogen sorption (BET), scanning electron microscopy (SEM) and solid-phase extraction (SPE) to plot adsorption isotherms.

The use of enzyme-coupled magnetic nanoparticles for studying the spectra of unusual substrates of mushroom tyrosinase by direct surface-assisted laser desorption/ionisation and high-resolution electrospray ionisation quadrupole-quadrupole-time-of-flight mass spectrometry.

Rationale: Tyrosinase-coupled magnetic particles (EMPs) were used to demonstrate that resorcinol-containing tyrosinase inhibitors are oxidised by tyrosinase only in the presence of the enzyme's classic substrate. This shows the potential for the application of EMPs as a non-organic matrix for monitoring enzymatic conversion of a novel substrate family directly on-the-spot, principally due to minimal enzyme requirement per analysis.

Methods: Tyrosinase was covalently coupled to core-shell-type silica-coated iron oxide magnetic nanoparticles (EMPs) that were applied as non-organic SALDI matrix suitable for studying low-mass compounds using a classic matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometer.

Evaluation of molecularly imprinted polymers using 2',3',5'-tri-O-acyluridines as templates for pyrimidine nucleoside recognition.

In this paper, we describe the synthesis and evaluation of molecularly imprinted polymers (MIPs), prepared using 2',3',5'-tri-O-acyluridines as 'dummy' templates, for the selective recognition of uridine nucleosides. The MIPs were synthesised using a non-covalent approach with 2,6-bis-acrylamidopyridine (BAAPy) acting as the binding monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The MIPs were evaluated in terms of capacity, selectivity and specificity by analytical and frontal liquid chromatography measurements.

Comparison of monolithic capillary electrochromatography and micellar electrokinetic chromatography for the separation of polycyclic aromatic hydrocarbons.

Atmospheric pollution of anthropic origin is recognized as a major risk factor for health, in particular for respiratory and cardio-vascular systems. Among these pollutants, polycyclic aromatic hydrocarbons (PAHs) are placed on the list of US Environmental Protection Agency (EPA) as 'priority' pollutants and four of them are assigned as potential carcinogens by The International Agency for Research on Cancer (IARC). In the present work two capillary techniques-micellar electrokinetic chromatography (MEKC) and monolithic capillary electrochromatography (CEC)-were compared for the separation of eleven PAHs.

Enzyme-coupled nanoparticles-assisted laser desorption ionization mass spectrometry for searching for low-mass inhibitors of enzymes in complex mixtures.

In this report, enzyme-coupled magnetic nanoparticles (EMPs) were shown to be an effective affinity-based tool for finding specific interactions between enzymatic targets and the low-mass molecules in complex mixtures using classic MALDI-TOF apparatus. EMPs used in this work act as nonorganic matrix enabling ionization of small molecules without any interference in the low-mass range (enzyme-coupled nanoparticles-assisted laser desorption ionization MS, ENALDI MS) and simultaneously carry the superficial specific binding sites to capture inhibitors present in a studied mixture. We evaluated ENALDI approach in two complementary variations: 'ion fading' (IF-ENALDI), based on superficial adsorption of inhibitors and 'ion hunting' (IH-ENALDI), based on selective pre-concentration of inhibitors.

Combination of computational methods, adsorption isotherms and selectivity tests for the conception of a mixed non-covalent-semi-covalent molecularly imprinted polymer of vanillin.

A novel molecularly imprinted polymer (MIP) for vanillin was prepared by photo initiated polymerization in dichloromethane using a mixed semi-covalent and non-covalent imprinting strategy. Taking polymerisable syringaldehyde as "dummy" template, acrylamide was chosen as functional monomer on B3LYP/6-31+G(d,p) density functional theory computational method basis with counterpoise. The binding parameters for the recognition of vanillin on imprinted polymers were studied with three different isotherm models (Langmuir, bi-Langmuir and Langmuir-Freundlich) and compared.

Synthesis of water-compatible imprinted polymers of in situ produced fructosazine and 2,5-deoxyfructosazine.

Fructosazine and 2,5-deoxyfructosazine are two natural chemicals with various applications as flavoring agents in food and tobacco industry; the 2,5-deoxyfructosazine has also anti-diabetic and anti-inflammatory activities. In order to quantify these compounds in natural samples such as plant or food, we have developed a selective technique based on a water-compatible molecularly imprinted polymer (MIP). MIPs are prepared with a covalent approach from 2,5-deoxyfructosazine as template formed in situ by the self-condensation of glucosamine with vinylphenyl boronic acid, taken as catalyst and covalent monomer during the pre-complexation step.

Continuous-flow step gradient mass spectrometry based method for the determination of kinetic parameters of immobilized mushroom tyrosinase in equilibrating conditions: comparison with free enzyme.

A mass spectrometry (MS)-based methodology for enzymatic assay in equilibrium conditions was designed and evaluated. This on-line assay involves the introduction of a continuous-flow step gradient (CFSG) of a substrate solution in the column containing immobilized enzyme and the simultaneous tracking of the product formation. We showed that the constant concentration of substrate in the entire bioreactor for an appropriate duration ensures the equilibration of the studied enzyme (mushroom tyrosinase).