Occurrence of Regulated and Emerging Iodinated DBPs in the Shanghai Drinking Water

10.1371/journal.pone.0059677PLoS ONE83

Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pools

37 páginas, 1 figura, 4 tablas.-- PDF con material suplementario.[BACKGROUND]: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending.[OBJECTIVES]: To evaluate whether swimming in pools is associated with biomarkers of genotoxicity.[METHODS]: We collected blood, urine, and exhaled air samples from 49 non-smoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes in exhaled breath and changes in the following biomarkers: micronuclei and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 h after swimming, urine mutagenicity (Ames assay) before and 2 h after swimming, and micronuclei in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or DBP metabolism.[RESULTS]: After swimming, the total concentration of the four trihalomethanes in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with exhaled concentrations of the brominated trihalomethanes (p = 0.03 for CHCl2Br, p = 0.05 for CHClBr2, p = 0.01 for CHBr3) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming in association with the concentration of exhaled CHBr3 (p = 0.004). No significant associations with changes in micronucleated urothelial cells were observed.[CONCLUSIONS]: Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.Research supported by Plan Nacional Grant SAF2005-07643-C03-01/02/03, Spain and FIS CP06/00341, Spain. CM Villanueva supported by the ISCIII (CP06/00341), Spain, L Font-Ribera by a predoctoral fellowship (FI06/00651), Spain, and D Liviac by a postgraduate fellowship UAB (PIF409-009), Barcelona.Peer reviewe

What’s in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water

38 páginas, 2 figuras, 4 tablas.-- PDF con material suplementario.[BACKGROUND]: Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity.[OBJECTIVES]: We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine, and we determined the mutagenicity of the waters to compare to the analytical results.[METHODS]: We used gas chromatography (GC)/mass spectrometry (MS) to measure THMs in water and GC with electron capture detection (ECD) for air, low and high resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity in the Salmonella mutagenicity assay.[RESULTS]: We identified more than 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in the brominated vs. chlorinated pool waters, but many brominated DBPs were also identified in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~1200 revertants/L-eq in strain TA100 –S9 mix).[CONCLUSIONS]: This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.This research was supported by EPA’s intramural research program and the Spanish grants SAF2005-07643-C03-01 (Plan Nacional) and CP06/00341 (Fondo de Investigación Sanitaria). CMV and LFR have, respectively, a contract and a predoctoral fellowship by the Instituto de Salud Carlos III (CP06/00341, FI06/00651). CL acknowledges a grant from the Agreement between Santander-Central Hispano and CSIC.Peer reviewe

Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS

Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes

Sirtuin 1 (Sirt1), a NAD[superscript +]-regulated deacetylase with numerous known positive effects on cellular and whole-body metabolism, is expressed in the renal cortex and medulla. It is known to have protective effects against age-related disease, including diabetes. Here we investigated the protective role of Sirt1 in diabetic renal damage. We found that Sirt1 in proximal tubules (PTs) was downregulated before albuminuria occurred in streptozotocin-induced or obese (db/db) diabetic mice. PT-specific SIRT1 transgenic and Sirt1 knockout mice showed prevention and aggravation of the glomerular changes that occur in diabetes, respectively, and nondiabetic knockout mice exhibited albuminuria, suggesting that Sirt1 in PTs affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein Claudin-1 by SIRT1-mediated epigenetic regulation in podocytes contributed to albuminuria. We did not observe these phenomena in 5/6 nephrectomized mice. We also demonstrated retrograde interplay from PTs to glomeruli using nicotinamide mononucleotide (NMN) from conditioned medium, measurement of the autofluorescence of photoactivatable NMN and injection of fluorescence-labeled NMN. In human subjects with diabetes, the levels of SIRT1 and Claudin-1 were correlated with proteinuria levels. These results suggest that Sirt1 in PTs protects against albuminuria in diabetes by maintaining NMN concentrations around glomeruli, thus influencing podocyte function.Japan. Ministry of Education, Culture, Sports, Science and Technology (Grant 22790800

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells

Background:In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species.Method:The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout.Results:Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis.Conclusions:This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders

Optimization, Application, and Interpretation of Lactate Dehydrogenase Measurements in Microwell Determination of Cell Number and Toxicity

The lactate dehydrogenase (LDH) assay was addressed for its sensitivity, disturbances by foaming, and cell number and size. Cells were from a U-251 MG grade IV human glioblastoma brain tumor cell line used in 100-µl well volumes. Cells were counted by microscopy and Coulter counting; assays were LDH or trypan blue. The results indicate increased 490 nm signals (level, variance) by using phenol red or by increasing fetal bovine serum from 5% to 10%. The data also indicate that defoaming results in reduced variances ranging from a factor of 2 at 1–3 units of absorption, up to a factor of 4–5 at <1 units of absorption. Coulter counting indicated a decrease in cell volume with increasing end-point cell density, attributed to general shrinking at increasing density. In comparisons, total LDH was considered relative to both cell total volume and cell numbers. The result suggests that total LDH should be regarded as reflecting cell total volume rather than cell numbers. In a comparative Cu exposure test, signals of both LDH and a sodium salt of 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) decreased with increasing Cu supply, while bromodeoxyuridine signals remained largely unaffected. The data show the differences in responses in cell viability and proliferation, but, above all, indicate that LDH should be expressed on a per cell volume basis rather than per cell, to avoid the problem that mere density effects contribute to signals on compound or metal toxicity.RST/Radiation, Science and TechnologyApplied Science