Colorectal cancer and inflammatory bowel diseases share common salivary proteomic pathways.

Inflammatory bowels diseases (IBD) are high risk conditions for colorectal cancer (CRC). The discovery of IBD and CRC noninvasive protein/peptide biomarkers using saliva and feces was the aim of this study involving 20 controls, 25 IBD (12 Crohn's Disease-CD), 37 CRC. By untargeted proteomic (LTQ-Orbitrap/MS), a total of 152 proteins were identified in saliva. Absent in controls, 73 proteins were present in both IBD and CRC, being mainly related to cell-adhesion, cadherin-binding and enzyme activity regulation (g-Profiler). Among the remaining 79 proteins, 14 were highly expressed in CD and 11 in CRC. These proteins clustered in DNA replication/expression and innate/adaptive immunity. In stool, endogenous peptides from 30 different proteins were identified, two being salivary and CD-associated: Basic Proline-rich Protein 1 (PRBs) and Acidic Proline-rich Phosphoprotein. Biological effects of the PRBs-related peptides GQ-15 and GG-17 found in CD stool were evaluated using CRC cell lines. These peptides induced cell proliferation and activated Erk1/2, Akt and p38 pathways. In conclusion, the salivary proteome unveiled DNA stability and immunity clusters shared between IBD and CRC. Salivary PRB-derived peptides, enriched in CD stool, stimulate CRC cell proliferation and the pro-oncogenic RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways suggesting a potential involvement of PRBs in IBD and cancer pathogenesis.

Validation of a radial diffusive sampler for measuring occupational exposure to 1,3-butadiene.

1,3-Butadiene (BD) is a major industrial chemical used in the manufacture of rubbers and latexes; it is also a ubiquitous environmental pollutant whose major source is traffic. Occupational exposure to (BD) can occur both during its production and during its use as a raw material. The objective of the study was the laboratory and field validation of a new diffusive sampler for BD. The nominal sampling rate of the Radiello diffusive sampler filled with Carbopack X is 30.5 cm(3)/min, at 0.177 mg/m(3), 20 °C and 50% relative humidity (RH), for an 8-h exposure time. A model can be used for calculating the sampling rate as a function of temperature, time and RH. The concentration does not affect the sampling rate above 30 µg/m(3). The measurement uncertainty (k=2), calculated both by laboratory data and by field comparison according to International Standard Organization (ISO) 13752, satisfies the EN 482:2006 requirement for measurements between 0.1 and 0.5 times the threshold limit value-time weighted average (TLV-TWA) (uncertainty<50%). For field validation study, 38 workers exposed to BD and 20 administrative employees, as the control group, underwent environmental and biological monitoring. Personal exposure to BD was measured by diffusive samplers (Radiello) in comparison with active samplers. The BD exposure levels detected for the exposed subjects were low (mean 0.059, range <0.010-1.340 mg/m(3)) but higher than the controls levels, all below 0.010 mg/m(3). The comparison between diffusive and active (pumped) air sampling showed a good correlation, with no systematic deviation from the ideal values of the intercept and slope of the optimized regression line. The concentrations of two biomarkers were also determined on urine samples, collected at the end of the work-shift: unchanged BD, by GC-MS, and the metabolite dihydroxybutylmercapturic acid (DHBMA), by HPLC-MS/MS. The urinary excretion of the biomarkers was on average higher in the exposed group (urinary BD: mean 8.8, range <1-48.1 ng/l; DHBMA: mean 0.232, range 0.016-0.572 mg/l) than in controls (urinary BD: mean 6.4, range 2.6-14.5 ng/l; DHBMA: mean 0.205, range 0.037-0.602 mg/l), but a statistically significant difference was achieved only for unchanged BD and not for DHBMA. In conclusion, the environmental monitoring measured by diffusive samplers (Radiello) appears to be a reliable method for the assessment of exposure to low levels of airborne BD and a convenient alternative to the conventional active sampling.

Correlation between environmental and biological monitoring of exposure to benzene in petrochemical industry operators.

The present work was aimed to study in petrochemical industry operators the correlation, if any, between environmental exposure to low levels of benzene and two biological exposure indexes in end-shift urine, i.e. trans, trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA). Exposure to benzene was assessed in 133 male subjects employed in outdoor operations in a petrochemical plant, using personal passive-diffusive air samplers worn at the breathing zone; adsorbed benzene was determined by GC-FID analysis. S-PMA was determined by a new HPLCMS/MS method, after (quantitative) acidic hydrolysis of the cysteine conjugate precursor. t,t-MA was measured by an HPLC-UV method. Smoking habits were assessed by means of a self-administered questionnaire. Both environmental and biological monitoring data showed that benzene exposure of petrochemical industry operators was low (mean values were 0.014ppm, 101mug/g creat, and 2.8mug/g creat, for benzene, t,t-MA, and S-PMA, respectively) if compared with the ACGIH limits. Cigarette smoking was confirmed to be a strong confounding factor for the urinary excretion of both metabolites: statistically significant increases of t,t-MA and S-PMA levels were recorded in smokers when compared to non-smokers (p<0.0001). The best correlation found was that between exposure to benzene and S-PMA levels, particularly in non-smokers. This was partly due to the hydrolysis of the S-PMA precursor N-acetyl-S-(1,2-dihydro-2-hydroxyphenyl)-l-cysteine, a crucial step of the new analytical method used, which indeed reduced the variability of the results by means of an improved standardization of this critical preanalytical factor. A weaker correlation was found between exposure to benzene and t,t-MA, possibly explained by the fact that the latter is also a metabolite of sorbic acid, a common diet component. In summary, even at such low levels of exposure, urinary metabolites proved to be a useful tool for assessing individual occupational exposure to benzene, S-PMA appearing to be a more specific biomarker than t,t-MA, particularly in non-smokers.

Biological indices of kidney involvement in personnel exposed to sevoflurane in surgical areas.

BACKGROUND: Fluoride, a main metabolite, and one degradation product of sevoflurane (SEV), called Compound A, are known to cause kidney effects in experimental animals. Other than in volunteers and patients, no research is available on exposed workers. The possible effects on the kidney in workers exposed in surgical areas were studied. METHODS: Subjects exposed to SEV and nitrous oxide (N(2)O) in surgical areas (N = 61) using open (N = 25) or semi-closed (N = 36) circuits were submitted to biological monitoring. The same biological indices were determined in 43 controls also. Sevoflurane (SEVU), nitrous oxide (N(2)OU), total urinary proteins (TUP), N-acetyl-beta-D-glucosaminidase (NAGU), and glutamine synthetase (GSU) were measured in urine. RESULTS: The mean values of environmental exposure were 31.3 ppm (range 0.9-111.6 ppm) for N(2)O and 0.28 ppm (range 0-1.88 ppm) for SEV. Exposed subjects had significantly higher excretion of TUP; a higher, not significant, excretion of GSU was also observed in subjects using open circuits. A significant correlation was found in all exposed subjects between NAGU and SEVU (r = 0.303, P < 0.05), GSU and N(2)OU (r = 0.382, P < 0.01) and, especially, GSU and SEVU (r = 0.650, P < 0.001). These correlations appeared to be influenced by the use of open circuits; infact, NAGU was well correlated to N(2)OU (r = 0.770, P < 0.001) and SEVU (r = 0.863, P < 0.001); GSU to N(2)OU (r = 0.468, P < 0.05) and SEVU (r = 0.735, P < 0.001). CONCLUSIONS: Results show that no relevant effect on the kidney is present for the levels of exposure studied. Nevertheless, correlation between dose and response urinary indices supports that SEV, other than N(2)O, may influence kidney function, especially when open circuits are used.