Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic diseases, diabetes, infertility, cancers and immunotoxicity. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 257 differentially modulated probe sets, identifying 221 well characterized genes.

Measurement of S-methylcysteine and S-methyl-mercapturic acid in human urine by alkyl-chloroformate extractive derivatization and isotope-dilution gas chromatography-mass spectrometry.

S-methylcysteine (SMC) is a minor amino acid naturally excreted in human urine, a protective agent against oxidative stress and a biotransformation product of the fumigant biocide methyl bromide and of nicotine. A metabolic source of SMC is catabolism of the repair catalytic protein MGMT (EC 2.1.

Occupational stress is associated with impaired work ability and reduced quality of life in patients with chronic kidney failure.

Background: About 300,000 patients in the United States with Chronic Kidney Failure (CKF) are of working age, but up to 70% lose their job within the first year of renal replacement therapy .No study has examined how work ability and perceived health are influenced by the subjects' adjustment to their job. We assessed the association of occupational stress (Effort-Reward Imbalance, ERI),work ability (WAI) and health-related quality of life (QoL) in hemodialysis.

Toward an "omic" physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds.

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g.

Thiol-disulfide redox equilibria of glutathione metaboloma compounds investigated by tandem mass spectrometry.

The thiol group of cysteine plays a pivotal role in structural and functional biology. We use mass spectrometry to study glutathione-related homo- and heterodimeric disulfides, aiming at understanding the factors affecting the redox potentials of different disulfide/thiol pairs. Several electrospray ionization (ESI)-protonated disulfides of cysteamine, cysteine, penicillamine, N-acetylcysteine, N-acetylpenicillamine, gammaGluCySH, HSCyGly, and glutathione were analyzed on a triple quadrupole instrument to measure their energy-resolved tandem mass spectra.

Environment And Genetics in Lung cancer Etiology (EAGLE) study: an integrative population-based case-control study of lung cancer.

Background: Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease.

A study of the glutathione metaboloma peptides by energy-resolved mass spectrometry as a tool to investigate into the interference of toxic heavy metals with their metabolic processes.

To better understand the fragmentation processes of the metal-biothiol conjugates and their possible significance in biological terms, an energy-resolved mass spectrometric study of the glutathione conjugates of heavy metals, of several thiols and disulfides of the glutathione metaboloma has been carried out. The main fragmentation process of gamma-glutamyl compounds, whether in the thiol, disulfide, thioether or metal-bis-thiolate form, is the loss of the gamma-glutamyl residue, a process which ERMS data showed to be hardly influenced by the sulfur substitution. However, loss of the gamma-glutamyl residue from the mono-S-glutathionyl-mercury (II) cation is a much more energetic process, possibly pointing at a strong coordination of the carboxylic group to the metal.

Electrospray ionization and triple quadrupole tandem mass spectrometry study of some biologically relevant homo- and heterodimeric cadmium thiolate conjugates.

A series of 19 compounds of general formula R1S-Cd-SR2, R1, and R2, being some biologically relevant thiol amino acids and peptides, were prepared by direct reaction of cadmium(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of stoichiometric 1:2 Cd-thiol systems containing either an individual thiol or equimolar mixtures of two different thiols featured several Cd-containing signals, although at much lesser intensity than in the previously reported experiments with mercury(II) (J.

Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs.

Objectives: This study evaluates by comet assay the induction of early DNA damage in healthcare workers of an oncology hospital regularly handling antineoplastic drug mixtures. The aim was to identify a suitable biomarker of DNA damage by exposure to low levels of such drugs.

Methods: We studied 12 day hospital nurses and 13 oncology ward nurses who performed up to 300 and up to 35 drug administrations per week, respectively, and five pharmacy employees who regularly prepared mixtures of antineoplastic agents.

Polyurethane foam chips combined with liquid chromatography in the determination of unmetabolized polycyclic aromatic hydrocarbons excreted in human urine.

A method suitable for the determination of unmetabolized polycyclic aromatic hydrocarbons (PAHs) excreted at trace levels (ng/L) in human urine for the monitoring of exposure of the general population to PAH contamination was developed. PAHs were determined, after enrichment by solid-phase extraction on polyurethane foam (PUF) chips, by HPLC with fluorescence detection. Different parameters affecting analyte extraction to the PUF, including urine salting-out and organic additives, and optimization of conditions for clean-up and desorption have been investigated.

Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.

Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices.

Assay of urinary alpha-fluoro-beta-alanine by gas chromatography-mass spectrometry for the biological monitoring of occupational exposure to 5-fluorouracil in oncology nurses and pharmacy technicians.

The validation of an analytical method for the measurement of the unnatural amino acid alpha-fluoro-beta-alanine (AFBA), the main metabolite of the antineoplastic drug 5-fluorouracil (5FU), in urine for the biological monitoring of the exposure of hospital workers to the drug when preparing the therapeutical doses and administering to cancer patients is described. The method employed a two-step extractive derivatization of the analyte from urine to the N-trifluoroacety-n-butyl ester derivative and detection by selected-ion monitoring gas chromatography-mass spectrometry of structurally specific fragments. The limit of detection was 20 ng/mL with quantification accuracy better than +/-20% and precision (CV%) better than +/-20% in the range 0.

Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure.

This research compared the capability of urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA) and benzene excreted in urine (U-benzene) to monitor low benzene exposure and evaluated the influence of smoking habit on these indices. Gasoline attendants, urban policemen, bus drivers and two groups of referents working in two large Italian cities (415 people) were studied. Median benzene exposure was 61, 22, 21, 9 and 6 microg/m3, respectively, with higher levels in workers than in referents.

The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene.

S-Phenylmercapturic acid (S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione. S-PMA may be determined by GC, HPLC (UV or fluorescence detection), GC-MS, LC-MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1 microg/l urine or below.

Volatile organic compounds produced during the aerobic biological processing of municipal solid waste in a pilot plant.

The volatile organic carbon (VOC) and odours emitted during the aerobic biological processing of municipal solid waste (MSW) was studied in a pilot-scale reactor. VOCs were detected by different techniques on solid waste samples and the outlet air stream, before and after a biofilter. Organic compounds (alpha-pinene, beta-myrcene, D-limonene) were also measured in condensate water and leachate from the process.

Characterization of the disulfides of bio-thiols by electrospray ionization and triple-quadrupole tandem mass spectrometry.

Glutathione and other intracellular low molecular mass thiols act both as the major endogenous antioxidant and redox buffer system and, as recently highlighted, as an important regulator of cellular homeostasis. Such cellular functions are mediated by protein thiolation, a newly recognized post-translational modification which involves the formation of mixed disulfides between GSH and key disulfide-linked Cys residues in the native protein structure. It is also well known that thiol-seeking heavy metals, such as mercury, cadmium and lead, may interfere in this regulatory system, thus disrupting the cellular functioning.

Molecular characterization of homo- and heterodimeric mercury(II)-bis-thiolates of some biologically relevant thiols by electrospray ionization and triple quadrupole tandem mass spectrometry.

A series of 24 compounds of general formula R(1)S-Hg-SR(2), R(1) and R(2) being biologically relevant thiol-containing amino acids and peptides (cysteine, homo-cysteine, penicillamine, N-acetyl-cysteine, N-acetyl-penicillamine, cysteinyl-glycine, gamma-glutamyl-cysteine and glutathione) were prepared by direct reaction of mercury(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of equimolar mixtures of two different thiols reacting with a stoichiometric amount of mercury(II) show the peak clusters of the three theoretically expected bis-thiolato-mercury(II) complexes with relative intensities close to the theoretically expected 1:2:1 ratio, thus pointing at lack of substantial discrimination between the different thiols, the only observed exception being homo-cysteine, which is less reactive than cysteine and penicillamine.

Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans.

Carcinogenicity of 1,3-butadiene (BD) has been linked to its metabolic activation of genotoxic epoxides. The inherited variations in the activity of BD-metabolizing enzymes may be responsible for individual differences that modulate the effects of BD exposure. In this study, 40 Italian subjects (30 BD-exposed workers and 10 clerks) were investigated to evaluate the role of genetic polymorphism of cytochromes P450 2E1, microsomal epoxide hydrolase, glutathione transferases GSTM1, GSTP1, GSTT1, and alcohol dehydrogenase, on urinary N-acetyl-S-(3,4-hydroxybutyl)-L-cysteine (MI) and hemoglobin N-(2,3,4-trihydroxybutyl)-valine adducts (THBVal).