Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination.

The increased thyroid cancer incidence in volcanic areas suggests an environmental effect of volcanic-originated carcinogens. To address this problem, we evaluated environmental pollution and biocontamination in a volcanic area of Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven trace elements were measured by quadrupole mass spectrometry in the drinking water and lichens (to characterize environmental pollution) and in the urine of residents (to identify biocontamination) in the Mt. Etna volcanic area and in adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/10(5) inhabitants in the volcanic and the control areas, respectively. The increase was exclusively due to the papillary histotype. Compared with control areas, in the volcanic area many trace elements were increased in both drinking water and lichens, indicating both water and atmospheric pollution. Differences were greater for water. Additionally, in the urine of the residents of the volcanic area, the average levels of many trace elements were significantly increased, with values higher two-fold or more than in residents of the control area: cadmium (×2.1), mercury (×2.6), manganese (×3.0), palladium (×9.0), thallium (×2.0), uranium (×2.0), vanadium (×8.0), and tungsten (×2.4). Urine concentrations were significantly correlated with values in water but not in lichens. Our findings reveal a complex non-anthropogenic biocontamination with many trace elements in residents of an active volcanic area where thyroid cancer incidence is increased. The possible carcinogenic effect of these chemicals on the thyroid and other tissues cannot be excluded and should be investigated.

[Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological surveillance in areas with environmental pollution by natural or anthropogenic arsenic]. / Studi su marcatori di esposizione ed effetto precoce in aree con inquinamento da arsenico: metodi e risultati del progetto SEpiAs. Sorveglianza epidemiologica in aree interessate da inquinamento ambientale da arsenico di origine naturale o antropica (SEpiAS CCM 2010).

INTRODUCTION: Arsenic and its inorganic compounds are classified as carcinogenic to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated with both carcinogenic and non-carcinogenic effects. The risk assessment of exposures to low-moderate levels of environmental arsenic (As) is a challenging objective for research and public health. The SEpiAs study, funded by the Italian Ministry of Health (CCM), was carried out in four areas with arsenic pollution prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin, Taranto and Gela. MATERIALS AND METHODS: 271 subjects (132 men) aged 20-44, were randomly sampled stratifying by area, gender and age classes. Individual data on residential history, socio-economic status, environmental and occupational exposures, lifestyle and dietary habits, were collected through interviews using questionnaire. In urine samples of recruited subjects, the concentration of inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using inductively coupled mass spectrometer (DRCICP- MS), after chromatographic separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as markers of cardiovascular risk were measured The distributions of iAs and iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles and standard deviation (SD). The associations between As species and variables collected by questionnaire were evaluated by multiple regression analysis. RESULTS: Results showed a high variability of As species within and among areas. Gela and Taranto samples showed higher iAs concentration compared to Viterbo and Amiata. Subjects with iAs>1,5 µg/L or iAs+MMA+DMA>15 µg/L (thresholds suggested by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%), respectively. A positive association between iAs and use of drinking water emerged in the Viterbo sample, between iAs and occupational exposure in the Gela and Taranto samples. Fish consumption was associated with higher iAs concentration in the whole sample, and particularly in men of the Gela sample. Similar results were observed for iAs+MMA+DMA. Subjects with iAs or iAs+MMA+DMA values higher than the 95th percentile were 15 (6Taranto, 5 Gela, 3Viterbo, 1 Amiata). The relationships between iAs and organic species (methylation efficiency ratios) were different between sex in the four areas. The relevance of polymorphisms AS3MT Met287Thr, GST-T1, GST-M1, OGG1 was confirmed. The analysis of carotid intima-media-thickness showed normal values, but higher among man of Viterbo, Taranto and Gela areas. CONCLUSIONS: Results are informative of exposure to inorganic and organic As in large or at least non-negligible quotas of the samples. The SEpiAs results suggest a further deepening on routes of exposure to arsenic species, and support the recommendation to implement primary prevention measures to reduce population exposure.

Selenium fortification of an Italian rice cultivar via foliar fertilization with sodium selenate and its effects on human serum selenium levels and on erythrocyte glutathione peroxidase activity.

Selenium food fortification could be a cost-effective strategy to counteract the inadequacy of selenium intake among the Italian population. In this study, the effect of foliar fertilization with sodium selenate of an Italian rice cultivar and the increase of serum selenium and of erythrocyte glutathione peroxidase (GPx) activity after intake of fortified rice, have been evaluated. The effect of foliar fertilization with sodium selenate (50 g Se/ha) vs. water was studied. Moreover, in a randomized, double-blind study, 10 healthy women supplemented their usual diet with a daily dose of 80 g of Se-enriched-rice and 10 matched-women with 80 g of regular rice. Before, after 5 and 20 days of supplementation, serum Se and GPx-activity were evaluated. The mean selenium content in Se-enriched-rice was 1.64 ± 0.28 µg/g, while in regular rice it was 0.36 ± 0.15 µg/g (p < 0.001). A significant increase of serum Se and GPx-activity was observed only in the intervention group and only after 20 days. The results show that selenium fortification of rice can be achieved with foliar fertilization with sodium selenate and that the 20 days intake of this Se-enriched-rice increases the serum selenium levels and GPx-activity.

Arsenic exposure triggers a shift in microRNA expression.

Exposure to inorganic Arsenic (iAs) through drinking water is a major public health problem affecting most countries. iAs has been classified by the International Agency for Research on Cancer as Group 1: "Carcinogenic to humans". Although numerous studies have shown the related adverse effects of iAs, sensitive appropriate biomarkers for studies of environmental epidemiology are still required. The present work aims at investigate the role of microRNAs (miRNAs), powerful negative regulators of gene expression, playing a key role in many physiological and pathological cellular processes, in iAs exposure. To this end, we analyzed miRNA changes in expression profile triggered by iAs exposure in Jurkat cell line. We used microarray technology to profile the expression of miRNAs following 2 µmol/L sodium arsenite treatment at different time points. Moreover, we performed phenotypic analysis of iAs treated cells. Real Time Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and to assay expression modulation of selected relevant mRNAs. Finally, bioinformatics techniques were applied to reconstruct iAs-relevant molecular pathways and miRNA regulatory networks from the expression data. We report miRNAs modulated after iAs treatment in Jurkat cells. In particular, we highlight 36 miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs which we also validated by RT-PCR analysis. Computational analysis of lists of putative target genes for these 8 miRNAs points to an involvement in arsenic-response pathways, for a subset of them, that were analyzed by RT-PCR. Furthermore, iAs exposure reveals induction of cell cycle progression and the failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study provides a list of miRNAs whose expression levels are affected by iAs treatment, corroborating the importance of proceeding with the hunt for specific subset of miRNAs, which can serve as potential biomarkers of iAs effects with useful diagnostic value.

Allergological and toxicological aspects in a multiple chemical sensitivity cohort.

BACKGROUND: Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. METHODS: We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. RESULTS: The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 µg/L; mean in urine was 1.9 ± 2.5 µg/L; mean in scalp hair was 2.2 ± 2.5 µg/g; mean in saliva was 38.1 ± 52.1 µg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). CONCLUSIONS: Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.

Simultaneous measurement of doxorubicin and reduced metabolite doxorubicinol by UHPLC-MS/MS in human plasma of HCC patients treated with TACE.

A sensitive, selective, accurate and precise method for simultaneous quantification of doxorubicin (DOX) and doxorubicinol (DOXol) in human plasma of patients diagnosed as having intermediate stage unresectable hepatocellular carcinoma (HCC) was developed. The method was based on electrospray tandem mass spectrometry in selected reaction monitoring mode. DOX, DOXol and trofosfamide, an internal standard, were extracted from plasma by using a simple solid phase extraction (SPE) procedure after the addition of 0.1 M hydrochloric acid. A 200-µL aliquot of the extracted sample reconstituted in mobile phase was analyzed on a Zorbax SB-C18 UHPLC column (50 mm × 2.1 mm, 1.8 µm particle size) in 8 min. The mobile phase consisted of acetonitrile and 0.1% formic acid pH 4.5 (95:05 v/v). Good accuracy and precision of this method were demonstrated by determination of spiked plasma QC samples in four consecutive days. The SPE extraction recoveries ranged from 72.3 to 77.3% and 75.5 to 98.4% for doxorubicin and doxorubicinol, respectively. The intra-day and inter-day precisions were less than 11.4%. The limit of quantitation was 1.0 ng/mL for both compounds. The calibration curves of DOX and DOXol were analyzed by weighted linear regression with 1/x as a weighting factor. They were linear over the concentration range of 1.0-100.0 ng/mL with R(2) greater than 0.99. This developed method was successfully applied to study plasma pharmacokinetics in patients affected by HCC and treated with transarterial chemoemolization practices (TACEs) using HepaSphere™ pre-loaded with DOX in a standardized procedure.

Serum concentrations of persistent organic pollutants (POPs) in the inhabitants of a Sicilian city.

BACKGROUND: Polychlorinated biphenyls (PCBs) and organochlorine pesticides are common environmental contaminants that have been associated with human health problems. OBJECTIVES: To assess serum concentrations of several organochlorine contaminants in general population living in a city with an ancient agricultural tradition and to identify possible exposure sources in Sicily. METHODS: A cross-sectional study was conducted on 101 individuals. Each participant answered a face-to-face questionnaire submitted by well-trained personnel and provided a serum sample which was analyzed for the concentrations of PCBs, HCB, HCHs and DDTs by using gas-chromatography coupled with mass spectrometry. RESULTS: HCB, p,p'-DDE, PCB 138, PCB 153 and PCB 180 were detected in more than 80% of the study participants. The ng g(-1) lipid median concentrations were: 18.6 for HCB; 175.1 for p,p'-DDE; 22. for PCB 138; 32.5 for PCB 153 and 23.0 for PCB 180. PCB 153 and PCB 138, PCB 138 and PCB 180, PCB 153 and PCB 180, and p,p'-DDE and HCB showed a high correlation each other (p<0.05). HCB and p,p'-DDE concentrations were significantly higher in subjects >49 years old (adj-p=0.03 in 50-69 years old and adj-p<0.001 in >69 years old, respectively) whereas PCB 138, PCB 153 and PCB 180 concentrations were higher in males (adj-p=0.03), in subjects >69 years old (adj-p=0.04) and in current smokers (adj-p=0.04). CONCLUSIONS: The present study shows that serum concentrations of organochlorine compounds detected in subjects living in a small Sicilian city with ancient agricultural tradition are similar to those found in subjects living in urban areas of other countries. However, further investigations are needed to compare data from rural/urban areas in the same country, assessing correlations between serum concentrations of several chemical compounds and potential health effects in general population.

Serum pharmacokinetics in patients treated with transarterial chemoembolization (TACE) using two types of epirubicin-loaded microspheres.

AIM: The purpose of this study was the pharmacokinetic (PK) profile assessment in the serum of patients affected by hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) with drug-eluting beads. PATIENTS AND METHODS: This study included 20 patients, 12 treated with DC Bead® and 8 with HepaSphere Microsphere®, preloaded with epirubicin. No patient randomization was used for the inclusion in one group or in the other. Peripheral blood samples were obtained from all patients after the treatment, until 24 hours past the procedure. RESULTS: The pharmacokinetic study showed low peak serum epirubicin concentrations with greater drug exposure for the DC Bead® group (p<0.05). The highest drug concentration after microsphere injection was observed at 5 minutes in all 20 patients. In the time interval between 1 and 24 hours after TACE, persisting levels of epirubicin were detected in peripheral blood samples. CONCLUSION: A persistent and sustained drug elution for both types of microparticles was found.

Farmers' exposure to herbicides in North Italy: assessment under real-life conditions in small-size rice and corn farms.

Although rice and corn are two main cash crops in Lombardy (North Italy) and their cultivation involves several thousands of farmers, risk assessment of pesticide exposure is rarely done, especially in small and medium sized enterprises. With the use of pads for environmental monitoring (OECD protocol), of pre- and post-exposure 24h urine collection for biological monitoring and of hand wash for hands' exposure, we measured the exposure of 28 agricultural workers to propanil and terbuthylazine in real-life working conditions. In propanil applicators, median daily exposure on the clothes was 73.5µmol per worker, while the exposure on the skin was 22.4µmol. For terbuthylazine, these exposures were 37.2µmol and 0.86µmol per worker, respectively. Median excretion of the propanil metabolite (3,4-dichloroaniline) after exposure was 84nmol in 24h urine, and 13nmol for the metabolite of terbuthylazine. Risk assessment performed by comparing to the AOELs of the applied active ingredients with an estimated internal dose, obtained based on the measured levels of skin and hand exposure and the percentage of dermal absorption of the active ingredients considered showed that 4 propanil workers, and no terbuthylazine workers, were overexposed. Our study helps define and confirm relationships between different exposure determinants, which can be used in the development of tools for risk assessment of exposure to pesticides in small and medium sized enterprises.

Integration of biological monitoring, environmental monitoring and computational modelling into the interpretation of pesticide exposure data: introduction to a proposed approach.

Open field, variability of climatic and working conditions, and the use of complex mixtures of pesticides makes biological and environmental monitoring in agriculture, and therefore risk assessment and management, very complicated. A need of pointing out alternative risk assessment approaches, not necessarily based on measures, but simple, user-friendly and reliable, feasible also in the less advanced situations and in particular in small size enterprises, arises. This aim can be reached through a combination of environmental monitoring, biological monitoring and computational modelling. We have used this combination of methods for the creation of "exposure and risk profiles" to be applied in specific exposure scenarios, and we have tested this approach on a sample of Italian rice and maize herbicide applicators. We have given specific "toxicity scores" to the different products used and we have identified, for each of the major working phases, that is mixing and loading, spraying, maintenance and cleaning of equipment, the main variables affecting exposure and inserted them into a simple algorithm, able to produce "exposure indices". Based on the combination of toxicity indices and exposure indices it is possible to obtain semiquantitative estimates of the risk levels experienced by the workers in the exposure scenarios considered. Results of operator exposure data collected under real-life conditions can be used to validate and refine the algorithms; moreover, the AOEL derived from pre-marketing studies can be combined to estimate tentative biological exposure limits for pesticides, useful to perform individual risk assessment based on technical surveys and on simple biological monitoring. A proof of principle example of this approach is the subject of this article.

Occupational exposure to antineoplastic drugs in four Italian health care settings.

Exposure assessment of health care workers to antineoplastic drugs (ADs) is still an open issue since new, critical, and emerging factors may put pharmacists who prepare hazardous drugs or nurses who administer anti cancer agents to an increased risk of developing adverse health effects. Overall, eight pharmacies and nine patient areas have been surveyed in this study. Wipe and pad samples were experienced during the surveillance program in four Italian health care settings. Urine samples were collected from workers handling ADs. Cyclophosphamide (CP), ifosfamide (IF), and gemcitabine (GEM) were detected in all the work environments by using a LC-MS/MS method-based capable of analysing all the three drugs simultaneously. In total, 54% of wipe samples were positive for at least one drug and 19% of pad samples were shown to be contaminated by cyclophosphamide. Pharmacies were generally more contaminated than patient areas with the exception of one site where a nurse had an acute exposure during the cleaning-up of an hazardous drug solution spill. In total, 22 urine samples collected from pharmacists and 78 urine samples from nurses had no detectable concentrations of any antineoplastic drugs. Despite the adherence to the recommended safety practices residue contamination on surfaces and floors has continued to be assessed in all the investigated sites.

Occupational exposure to antineoplastic drugs in seven Italian hospitals: the effect of quality assurance and adherence to guidelines.

In health care facilities, dermal contact and inhalation are considered to be the main routes of exposure to cytotoxic antineoplastic drugs (ADs). Hand-to-mouth contamination or accidental needle sticks as well as events due to inadequate disposal may also contribute to exposure. In order to measure the extent of contamination, biological and environmental monitoring are essential tools for routine testing. Moreover, reliable sampling and analytical procedures are required. During the last decade, several methods have been developed and validated. The appropriate analytical techniques were used to quantify even very low levels of some of the more commonly used ADs, such as cyclophosphamide, 5-fluoruracil, taxol, anthracyclines, and platinum-compounds. The main objective of this study is to assess the adherence to existing standards of practice through an effective monitoring program, including environmental and biological measurements. In seven hospitals located in Northern-Central Italy, periodic surveys were scheduled to verify continuing compliance with guidelines over a 5-year period. All biological samples were found to be below detection limits and a progressive, significant decrease in workplace contamination was observed. Our results confirm that a cost-effective monitoring regime, including fast and simple sample pre-treatment procedures, simultaneous determination of the analytes and their metabolites, validated procedures including uncertainty evaluation, and periodic surveys, is the adequate approach for the collection of reliable exposure data and hence for effective intervention.

[microRNAs as biological indicators of environmental and occupational exposure to asbestos]. / I microRNA come indicatori biologici di esposizione ambientale e occupazionale ad amianto.

Malignant mesothelioma is an aggressive cancer refractory to current therapies, the incidence of which is expected to rise in the next decades. Exposure to asbestos is a well known risk factor, as InternationalAgency for Research and Cancer (IARC) classified this compound as group I (carcinogenic to humans). The lack of tumor biomarkers for diagnosis and medical survey plays a fundamental role for the development of a universally accepted therapeutic approach. In this review we evaluated the mechanism of asbestos carcinogenesis by analyzing activated oncogenes, genetic predisposition, and SV40 infection as cofactors. Therefore, interest has focused on microRNAs, 19-25 nucleotide-long single-stranded RNAs that negatively regulate gene expression by modulating translational efficiency of target genes involved in numerous cellular processes including development, differentiation, proliferation, apoptosis, and stress response. The analysis revealed a differential expression of miRNAs between mesothelioma and mesothelial cells, suggesting their potential role as oncogenes or tumor suppressor genes in mesothelioma oncogenesis. We have also investigated the role of polymorphism in the etiology and pathogenesis of mesothelioma, in order to evaluate the association between disease linked to asbestos exposure andgenetic variability. The identification of dysregulated miRNAs or frequent genetic polymorphisms as potential diagnostic biomarkers or as prognostic factors for malignant mesothelioma could facilitate the surveillance procedure of subjects exposed to asbestos.

Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver.

BACKGROUND: Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and for adequate preservation of liver function. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of the complications associated with TACE therapy and to correlate it with certain risk factors, either well-known or not yet evaluated. PATIENTS AND METHODS: A total of 330 chemoembolization procedures performed in 170 patients (117 males and 53 females) over a period of 64 months were retrospectively analysed. Among the patients, 123 had hepatocellular carcinoma, 10 had intrahepatic cholangiocarcinoma and 37 had hepatic metastases. The variables considered were: tumour histotype, bilioenteric anastomosis, previous or combined treatment with radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents, use of new drug-eluting microspheres, comorbidities such as diabetes, patient age and the presence of vascular anatomical variations. RESULTS: A total of 30 complications occurred in 27 procedures. The total complication rate per procedure was 9.1% and approximately 75% of patients had postembolization syndrome. The difference in the prevalence of complications was statistically significant in the group of diabetic patients (13.3%) compared to the remaining patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to those without stents (7.75%) (p = 0.027). CONCLUSION: These data show that diabetes mellitus and the presence of bilioenteric anastomosis are risk factors for developing complications after TACE. The use of new drug-eluting microspheres did not increase the risk of complications.