Retinal pigment epithelium (RPE) dysfunction and degeneration underlie the development of age-related macular degeneration (AMD), which is the leading cause of blindness worldwide. In this study, we investigated whether cerium oxide nanoparticles (CeO₂-NPs or nanoceria), which are anti-oxidant agents with auto-regenerative properties, are able to preserve the RPE. On ARPE-19 cells, we found that CeO₂-NPs promoted cell viability against H₂O₂-induced cellular damage. For the in vivo studies, we used a rat model of acute light damage (LD), which mimics many features of AMD. CeO₂-NPs intravitreally injected three days before LD prevented RPE cell death and degeneration and nanoceria labelled with fluorescein were found localized in the cytoplasm of RPE cells. CeO₂-NPs inhibited epithelial-mesenchymal transition of RPE cells and modulated autophagy by the down-regulation of LC3B-II and p62. Moreover, the treatment inhibited nuclear localization of LC3B. Taken together, our study demonstrates that CeO₂-NPs represent an eligible candidate to counteract RPE degeneration and, therefore, a powerful therapy for AMD.

Keywords: atrophic AMD; autophagy; light damage; nanoceria; nanomedicine; retinal pigment epithelium.

The possibility of eye exposure for workers participating in manufacturing of nanoparticles or consumers using products containing nanoparticles has been reported, but toxicity studies on the eye are scarce. In this study, cytotoxicity of five nanoparticles including silver, ceria, silica, titanium and zinc were tested using Statens Seruminstitut Rabbit Cornea (SIRC) cells. When cells were treated with nanoparticles with concentrations of 1-100 μg/mL for 24 hr, zinc oxide nanoparticles showed higher toxicity to cornea cells. LC₅₀ of zinc oxide nanoparticles was less than 25 μg/mL but those of other nanoparticles could not be calculated in this test, which means more than 100 μg/mL. Generation of reactive oxygen species was observed, and expression of apoptosis related biomarkers including Bax and Bcl-2 were changed after treatment of zinc oxide nanoparticles, while no other significant toxicity- related changes were observed in cornea cells treated with Ag, CeO₂, SiO₂ and TiO₂ nanoparticles.

N,N-bis(2-hydroxybenzyl)alkylamines, benzoxazine dimers, are the major product produced from benzoxazine monomers on mono-functional phenol by the one step ring opening reaction. Due to the metal responsive property of benzoxazine dimers, in this present work, N,N-bis(5-methyl-2-hydroxybenzyl)methylamine (MMD), N,N-bis (5-ethyl-2-hydroxybenzyl)methylamine (EMD), and N,N-bis(5-methoxy-2-hydroxybenzyl) methyl amine (MeMD), are considered as novel ligands for rare earth metal ion, such as cerium(III) ion. The complex formed when the clear and colorless solutions of cerium nitrate and benzoxazine dimers were mixed, results in a brown colored solution. The metal-ligand ratios determined by the molar ratio and the Job's methods were found to be in a ratio of 1:6. To clarify the evidence of the complex formation mechanism, the interactions among protons in benzoxazine dimers both prior to and after the formation of complexes were determined by means of (1)H-NMR, 2D-NMR and a computational simulation. The single phase ceria (CeO(2)) was successfully prepared by thermal decomposition of the Ce(III)-benzoxazine dimer complexes at 600 °C for 2 h, was then characterized using XRD. In addition, the ceria powder investigated by TEM is spherical with an average diameter of 20 nm.

Over the last decades, cerium oxide nanoparticles (CeO₂ NPs) have gained great interest due to their potential applications, mainly in the fields of agriculture and biomedicine. Promising effects of CeO₂ NPs are recently shown in some neurodegenerative diseases, but the mechanism of action of these NPs in Parkinson's disease (PD) remains to be investigated. This issue is addressed in the present study by using a yeast model based on the heterologous expression of the human α-synuclein (α-syn), the major component of Lewy bodies, which represent a neuropathological hallmark of PD. We observed that CeO₂ NPs strongly reduce α-syn-induced toxicity in a dose-dependent manner. This effect is associated with the inhibition of cytoplasmic α-syn foci accumulation, resulting in plasma membrane localization of α-syn after NP treatment. Moreover, CeO₂ NPs counteract the α-syn-induced mitochondrial dysfunction and decrease reactive oxygen species (ROS) production in yeast cells. In vitro binding assay using cell lysates showed that α-syn is adsorbed on the surface of CeO₂ NPs, suggesting that these NPs may act as a strong inhibitor of α-syn toxicity not only acting as a radical scavenger, but through a direct interaction with α-syn in vivo.

Little has been written about how regulatory bodies define and demonstrate accountability. This paper describes a substudy of a research project on accountability in healthcare. The aim was to increase understanding of how regulatory bodies perceive and demonstrate accountability to their stakeholders. Twenty-two semi-structured interviews were conducted with provincial/territorial CEOs from the two largest health professional regulatory bodies in Canada: medicine and nursing. The regulators indicated that accountability was essential to their mandates and provided the foundation for regulatory frameworks. However, they did not offer a common definition of accountability. They agreed that they were accountable to three constituencies: the public, government and their members. Regulators noted that protecting the public and meeting the demands of the government and their members creates tension. They were also concerned about maintaining independence in the regulatory role.

The toxicity of CeO2 NPs on an experimental freshwater ecosystem was studied in mesocosm, with a focus being placed on the higher trophic level, i.e. the carnivorous amphibian species Pleurodeles waltl. The system comprised species at three trophic levels: (i) bacteria, fungi and diatoms, (ii) Chironomus riparius larvae as primary consumers and (iii) Pleurodeles larvae as secondary consumers. NP contamination consisted of repeated additions of CeO2 NPs over 4 weeks, to obtain a final concentration of 1 mg/L. NPs were found to settle and accumulate in the sediment. No effects were observed on litter decomposition or associated fungal biomass. Changes in bacterial communities were observed from the third week of NP contamination. Morphological changes in CeO2 NPs were observed at the end of the experiment. No toxicity was recorded in chironomids, despite substantial NP accumulation (265.8 ± 14.1 mg Ce/kg). Mortality (35.3 ± 6.8%) and a mean Ce concentration of 13.5 ± 3.9 mg/kg were reported for Pleurodeles. Parallel experiments were performed on Pleurodeles to determine toxicity pathways: no toxicity was observed by direct or dietary exposures, although Ce concentrations almost reached 100 mg/kg. In view of these results, various toxicity mechanisms are proposed and discussed. The toxicity observed on Pleurodeles in mesocosm may be indirect, due to microorganism's interaction with CeO2 NPs, or NP dissolution could have occurred in mesocosm due to the structural complexity of the biological environment, resulting in toxicity to Pleurodeles. This study strongly supports the importance of ecotoxicological assessment of NPs under environmentally relevant conditions, using complex biological systems.

Cerium oxide nanoparticles (nanoceria) are regarded as one of the most promising inorganic antioxidants for biomedical applications. Considering nanoceria as a potential therapeutic agent, we aimed to develop a robust system for its intracellular delivery using layer-by-layer polyelectrolyte microcapsules. We have shown that citrate-stabilized cerium oxide nanoparticles can be effectively incorporated into the structure of polyelectrolyte microcapsules made from biodegradable and nonbiodegradable polymers. The structure and morphology of synthesized microcapsules were investigated and analyzed using confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and UV/vis spectroscopy. Results of experiments in vitro on B50 neuroblastoma cells confirmed nanoceria delivery into the cell while maintaining their antioxidant properties. The results presented confirm polyelectrolyte microcapsules to be an efficient intracellular delivery system for therapeutic nanoparticles.

Keywords: antioxidant activity; cell culture; cerium oxide nanoparticles; oxidative stress; polyelectrolyte microcapsules.

Ceria nanoparticles (CeO₂ NPs) are generally considered in various functional applications, such as catalysts in fuel cells, sensors, and antioxidant and oxidase-like enzymes in the biological environment. The CeO₂ NPs were synthesized using the E. globulus leaf extract-mediated hydrothermal technique. The synthesized NPs were characterized by various analytical instruments including powder X-ray diffractometer (PXRD), scanning electron microscope (SEM), transmission electron microscope (TEM) and dynamic light scattering (DLS) analysis. The XRD results showed an average NPs sizes of 13.7 nm. Cytotoxic study results showed an IC₅₀ value of 45.5 µg/L for A549 and 58.2 µg/L for HCT 116, indicating that CeO₂ NPs are more toxic to A549 compared to HCT116 cell lines. The generation of ROS was responsible for its cytotoxic activity against cancer cell lines. Specific surface area (40.96 m²/g) and pore diameter (7.8 nm) were measured using Brunauer-Emmett-Teller (BET) nitrogen adsorption-desorption isotherms. CeO₂ NPs with a high surface area were used as photocatalyst in degrading sunset yellow (SY) dye under UV-irradiation and 97.3% of the dye was degraded within 90 min. These results suggest that the synthesized CeO₂ NPs could be used as a good photocatalyst as well as a cytotoxic agent against human cancer cell lines.

A multistep sample preparation method was developed to separate metal-based engineered nanoparticles (ENPs) from biological samples. The method was developed using spiked zebrafish tissues and standard titanium dioxide (TiO₂) and cerium dioxide (CeO₂) ENPs. Single-particle inductively coupled plasma mass spectrometry was used to quantify the separated particles in terms of number concentration. This method demonstrated mass recoveries of more than 90% and did not strikingly alter the median particles size. High number recoveries were calculated for CeO₂ ENPs (>84%). Particle number recoveries were poor for TiO₂ ENPs (<25%), which could be due to the interference of ⁴⁸Ca with the measured isotope ⁴⁸Ti. The method was verified using zebrafish exposed to CeO₂ ENPs to test its applicability for nanotoxicokinetic investigations. Total mass of Ce and particle number concentration of CeO₂ ENPs were measured in different tissues. Notably, the mass-based biodistribution of Ce in the tissues did not follow the number-based biodistribution of CeO₂. Moreover, the calculated mass-based bioconcentration factors showed a different pattern in comparison to the number-based bioconcentration factors. Our findings suggest that considering mass as the sole dose-metric may not provide sufficient information to investigate toxicity and toxicokinetics of ENPs.

We reported a novel bimetallic cerium/copper-based metal organic framework (Ce/Cu-MOF) and its derivatives pyrolyzed at different temperatures, followed by exploiting them as the scaffold of electrochemical aptamer sensors for extremely sensitive detection of trace tobramycin (TOB) in human serum and milk. After the calcination at high temperature, the meal coordination centers (Ce and Cu) were transferred to metal oxides containing various chemical valences, such as Ce(III), Ce(IV), Cu(II) and Cu(0), which were embedded within the mesoporous carbon network originated from the organic ligands (represented by CeO₂/CuO_x@mC). Owning to the strong synergistic effect among the metal oxides, mesoporous carbon, and small cavities and open channels of MOF, the as-prepared CeO₂/CuO_x@mC nanocomposites not only possess good electrochemical activity but also exhibit strong bioaffinity toward the aptamer strands. By comparing the electrochemical biosensing peroformances using on the Ce/Cu-MOF- and the series of CeO₂/CuO_x@mC-based aptasensors, the constructed CeO₂/CuO_x@mC₉₀₀-based (calcinated at 900 °C) aptasensor exhibits an extremely low detection limit of 2.0 fg mL^-1 within a broad linear TOB concentration range from 0.01 pg mL^-1 to 10 ng mg L^-1. It demonstrates that the proposed aptasensor is substantially superior to those previously reported in the literature, along with high selectivity, good stability and reproducibility, and acceptable applicability in human serum and milk. Thereby, the newly fabricated aptasensing approach based on bimetallic CeO₂/CuO_x@mC has a considerable potential for the quantitative detection of antibiotics in the food safety and biomedical field.

In this work, we proposed a strategy that combined molecularly imprinted polymers (MIPs) and hybridization chain reaction into microfluidic paper-based analytical devices for ultrasensitive detection of target glycoprotein ovalbumin (OVA). During the fabrication, Au nanorods with a large surface area and superior conductibility were grown on paper cellulosic fiber as a matrix to introduce a boronate affinity sandwich assay. The composite of MIPs including 4-mercaptophenylboronic acid (MPBA) was able to capture target glycoprotein OVA. SiO₂@Au nanocomposites labeled MPBA and cerium dioxide (CeO₂)-modified nicked DNA double-strand polymers (SiO₂@Au/dsDNA/CeO₂) as a signal tag were captured into the surface of the electrode in the presence of OVA. An electrochemical signal was generated by using nanoceria as redox-active catalytic amplifiers in the presence of 1-naphthol in electrochemical assays. As a result, the electrochemical assay was fabricated and could be applied in the detection of OVA in the wide linear range of 1 pg/mL to 1000 ng/mL with a relatively low detection limit of 0.87 pg/mL (S/N = 3). The results indicated that the proposed platform possessed potential applications in clinical diagnosis and other related fields.

This study confirmed the inhibitory effects of clove essential oil (CEO) and eugenol (EUG) on the browning and relevant enzymes of fresh-cut lettuce, and examined associated mechanisms by inhibition kinetics and computational docking analysis. Fresh-cut lettuce was treated with 0.05% CEO and 0.05% EUG solutions, resulting in inhibition of the deterioration of texture quality and browning of the lettuce surface and interior. Compared with the controls, CEO and EUG significantly inhibited the activities of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD, all p<0.05). EUG suppressed PAL, PPO, and POD in vitro in a dose-dependent manner, with IC50 values of 5.4±0.9, 29.5±3.5, and 61.9±6.7mM, respectively. The binding and inhibition effects of EUG on PAL, PPO, and POD, determined by inhibition kinetics and computational docking analysis, established EUG as a competitive inhibitor of these browning-relevant enzymes.

In this paper, we investigated the primary reduction and oxygen replenishing processes over Mn substitutionally doped CeO(2)(111) surfaces by density functional theory with the on-site Coulomb correction (DFT + U). The results indicated that Mn doping could make the surface much more reducible and the adsorbed O(2) could be effectively activated to form superoxo (O(2)(-)) and/or peroxo species (O(2)(2-)). The Mn doping induced the Mn 3d-O 2p gap state instead of Ce 4f acting as an electrons acceptor and donor during the first oxygen vacancy formation and O(2) replenishing, which helped to lower the formation energy of the first and second oxygen vacancies to -0.46 eV and 1.40 eV, respectively. In contrast, the formation energy of a single oxygen vacancy in the pure ceria surface was 2.08 eV and only peroxo species were identified as the O(2) molecule adsorbed. Our work provides a theoretical and electronic insight into the catalytic redox processes of Mn doped ceria surfaces, which may help to understand the enhanced catalytic performances of MnO(x)-CeO(2) oxides, as reported in previous experimental works.

Capture and recycling of CO2 into valuable chemicals such as alcohols could help mitigate its emissions into the atmosphere. Due to its inert nature, the activation of CO2 is a critical step in improving the overall reaction kinetics during its chemical conversion. Although pure gold is an inert noble metal and cannot catalyze hydrogenation reactions, it can be activated when deposited as nanoparticles on the appropriate oxide support. In this combined experimental and theoretical study, it is shown that an electronic polarization at the metal-oxide interface of Au nanoparticles anchored and stabilized on a CeO(x)/TiO2 substrate generates active centers for CO2 adsorption and its low pressure hydrogenation, leading to a higher selectivity toward methanol. This study illustrates the importance of localized electronic properties and structure in catalysis for achieving higher alcohol selectivity from CO2 hydrogenation.

A general self-templating method is introduced to construct triple-shelled CeO₂ hollow microspheres, which are composed of tiny CeO₂ nanoparticles. When the triple-shelled CeO₂ hollow microspheres are used as photocatalysts for direct water oxidation with AgNO₃ as the electron scavenger, excellent activity and enhanced stability for O₂ evolution are achieved, in contrast with commercial CeO₂ nanoparticles, single-shelled CeO₂ hollow microspheres and double-shelled CeO₂ hollow microspheres. Such an outstanding performance is attributed to the unique properties of the triple-shelled CeO₂ hollow microspheres including more efficient multiple reflections of the incident light by the inner shells, the larger surface area and more active sites for improving separation of electron-hole pairs, and the more curved surfaces unfavorable for deposition of in situ generated Ag nanoparticles.

A series of Ce-Ti mixed-oxide catalysts were prepared by the sol-gel method for selective catalytic reduction (SCR) of NO with ammonia as reductant. These catalysts were characterized by XRD, BET, and XPS techniques. The experimental results show that the best Ce-Ti mixed-oxide catalyst yielded 98.6% NO conversion, and 100% N(2) selectivity at typical SCR reaction temperatures (300-400 degrees C) and the high gas hourly space velocity of 50,000 h(-1). As the Ce loading (the mass ratio of CeO(2)/TiO(2)) was increased from 0 to 0.6, NO conversion increased markedly, but decreased at higher Ce loading. The most active catalyst was obtained with a Ce loading of 0.6. The high activity might be attributed to high Ce loading, strong interaction between Ce and Ti, high concentration of amorphous Ce on the catalyst surface, or the increase of chemisorbed oxygen or/and weakly bonded oxygen species, resulting from the presence of Ce(3+) after Ce addition. The effect of the calcination temperature was also investigated, and the optimal calcination temperature was 500 degrees C. The presence of oxygen played an essential role in NO reduction, and the activity of the Ce(0.6)Ti catalyst was not depressed when oxygen concentration was higher than 1%. The effect of SO(2) and H(2)O on the activity of the Ce(0.6)Ti catalyst was bound up with the reaction temperature.

OBJECTIVE

To quantify the progression of visual field loss in participants with open angle glaucoma.

METHODS

Cluster random samples of 3271 participants participated in this study. Each participant underwent a standardized ophthalmic examination, which included intraocular pressure measurement, Humphrey 24-2 Fastpac visual field testing and stereophotography of the optic disc. At baseline 118 participants were identified as possible, probable or definite open angle glaucoma and 74 (62.7%) of these were seen again at the follow-up examination. Progression of visual field loss was defined using three methods: the Advanced Glaucoma Intervention Study criteria, the modified Anderson criteria and the Blumenthal method.

RESULTS

In total, 49% of subjects showed progressive visual field loss with at least one method. The Blumenthal criteria yielded the highest rate of progression (37%), followed by the modified Anderson method (33%) and the Advanced Glaucoma Intervention Study method (16%). The progressive visual field loss was associated with baseline glaucoma status (P = 0.02); 65% of the definite glaucoma progressed, compared with 57% of the probable glaucoma and 25% of the possible glaucoma. Participants who had been previously diagnosed with glaucoma had a higher rate of progression (54%) when compared with those who had not been diagnosed previously (47%). In total, 50% (four of eight) of those receiving glaucoma medication at baseline had progressive visual field loss; all were in the definite glaucoma category.

CONCLUSIONS

Despite use of glaucoma medications the majority of glaucoma patients managed by their regular ophthalmologist experienced progressive visual field loss over a 5-year period.

It is becoming more feasible to use nano-enabled agricultural products such as nanofertilizers and nanopesticides to improve the efficiency of agrochemical delivery to crop plants. Experimental results have shown that nano-agrochemicals have great potential for reducing the environmental impact of traditional agrochemicals while simultaneously significantly increasing crop production. However, emerging data suggest that nano-enabled products are not only capable of increasing yield, but also result in alterations in crop quality. Variation in proteins, sugars, starch content, as well as in metallic essential elements have been reported. Verbi gratia, albumin, globulin, and prolamin have been significantly increased in rice exposed to CeO₂ engineered nanoparticles (ENPs), while CeO₂, CuO, and ZnO ENPs have increased Ca, Mg, and P in several crops. Conversely, reductions in Mo and Ni have been reported in cucumber and kidney beans exposed to CeO₂ and ZnO engineered nanomaterials, respectively. However, reports on specific effects in human health due to the consumption of agricultural products obtained from plants exposed to nano-agrochemicals are still missing.

Keywords: Crop quality; Engineered nanomaterials; Human health; Nanofertilizers; Nanopesticides.

Air-liquid interface (ALI) systems have been widely used in recent years to investigate the inhalation toxicity of many gaseous compounds, chemicals, and nanomaterials and represent an emerging and promising in vitro method to supplement in vivo studies. ALI exposure reflects the physiological conditions of the deep lung more closely to subacute in vivo inhalation scenarios compared to submerged exposure. The comparability of the toxicological results obtained from in vivo and in vitro inhalation data is still challenging. The robustness of ALI exposure scenarios is not yet well understood, but critical for the potential standardization of these methods. We report a cause-and-effect (C&E) analysis of a flow through ALI exposure system. The influence of five different instrumental and physiological parameters affecting cell viability and exposure parameters of a human lung cell line in vitro (exposure duration, relative humidity, temperature, CO₂ concentration and flow rate) was investigated. After exposing lung epithelia cells to a CeO₂ nanoparticle (NP) aerosol, intracellular CeO₂ concentrations reached values similar to those found in a recent subacute rat inhalation study in vivo. This is the first study showing that the NP concentration reached in vitro using a flow through ALI system were the same as those in an in vivo study.

<strong class="sub-title"> Keywords: </strong> <em>CeO</em>2; air–liquid interface system; cause-and-effect analysis; inhalation toxicology; nanoparticles; standardization.

BACKGROUND

A variety of studies have indicated that rural communities have fewer mental health services and professionals than their urban counterparts. This study will examine the shortages of mental health professionals in rural communities as well as the impact of inadequate mental health services access on rural hospitals.

METHODS

A sample frame of 1162 rural hospitals was compiled, and a two-page survey was mailed to each hospital Chief Executive Officer (CEO).

RESULTS

Of the 1162 surveys mailed, 228 were returned. The majority of CEOs agreed that there was a shortage of mental health professionals, that referral centers were too distant, and that there were many barriers to care including infrastructure, poverty, and substance abuse. Solutions offered by CEOs included telemedicine and residency training programs.

CONCLUSIONS

This study shows that many rural areas have great need for more mental health professional recruitment and retention.

This study takes a first step toward examining the relationship between organizational characteristics and the perceived attitude toward health promotion in companies from the perspective of chief executive officers (CEOs). Data for the cross-sectional study were collected through telephone interviews with one CEO from randomly selected companies within the German information and communication technology (ICT) sector. Multivariate logistic regression analysis (LRA) was performed, and further LRA was conducted after stratifying on company size. LRA of data from a total of n = 522 interviews found significant associations between the attitude toward health promotion and the company's market position, its number of hierarchical levels, the percentage of permanent positions and the percentage of employees with an academic education. After stratification on company size, the association between the attitude toward health promotion and both market position and the percentage of employees with an academic education was still present in small companies. There were no significant relationships between the attitude toward health promotion and the structural characteristics of medium-sized and large companies. The preliminary results of the study indicate that a perceived attitude toward health promotion in companies can be explained, to a certain degree, by the intraorganizational characteristics analyzed. Our key findings highlight that efforts toward establishing a positive attitude toward health promotion should focus on small companies with a lower market position and a greater number of employees with a lower education level.

This investigation focuses on the impact of multi-institutional arrangements on the role of governing boards in limiting or enhancing the managerial autonomy of individual hospitals. Data from a 1979 Special Survey by the American Hospital Association (N = 4213) are used to examine governing board-administrator relationships as a function of the degree of autonomy and scope of responsibility of the hospital governing board. It is hypothesized that governing boards responsible for multiple hospitals or for multiple nonhospital organizations and those boards accountable to a higher organizational authority will exercise more formal control over hospital chief executive officers (CEOs) than will boards of single or autonomous hospitals. The analysis assumes that formal control by the governing board over the management function of the individual hospital is exercised partly through soliciting or limiting participation by hospital administrators in key policy decisions and through the evaluation of administrative performance. Therefore, it is anticipated that hospitals governed by boards with multiple responsibilities as well as hospitals governed by boards accountable to a higher authority will be (1) less likely to have CEOs who are members of the governing board executive committee, (2) more likely to have annual performance reviews of the CEO by the governing board, and (3) more likely to have such reviews conducted according to preestablished criteria. Study results provide general support for the hypotheses with respect to hospital boards with multiple responsibilities: the data suggest that such boards do exercise greater control over hospital administrators and these effects do appear to be stronger for hospitals in the private sector. Hospitals governed by boards accountable to a higher authority, however, are more likely to have CEOs who are members of the governing board executive committee--a pattern in direct opposition to that hypothesized. Furthermore, these boards are no more likely to conduct annual CEO performance reviews than are boards with more autonomy. Boards accountable to higher authorities are more likely, however, to use preestablished criteria when such reviews are conducted. This general pattern is similar whether hospital boards are accountable to religious authorities, to investor-owned corporate boards, or to the boards of not-for-profit multi-institutional systems. A different pattern emerges, however, for boards accountable to a state, county, or local government authority.(ABSTRACT TRUNCATED AT 400 WORDS)

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. 2-Chloroethylene oxide (CEO) and 2-chloroacetaldehyde (CAA), the metabolic intermediates of VCM, induce DNA damage which is mainly repaired by the nucleotide excision repair (NER) pathway. The XPD gene product and the related XPB protein are DNA helicases that are involved in transcription and NER. Polymorphisms of XPD have been implicated in chemical exposure-related health effects. In order to explore the mechanism of VCM-related health effects, a special matched case-control design (exposed workers with DNA damage and without damage) was used to investigate the association between the gene polymorphisms of XPD and DNA damage in 106 male and 44 female workers occupationally exposed to VCM. Exposure and anthropometrics information was collected through in-person interview. Such information was then used to calculate cumulative exposure doses of the workers. DNA damage in peripheral lymphocytes was measured by the single cell gel electrophoresis (SCGE) assay that identified DNA strand breaks. Genomic DNA from lymphocytes was used in genotyping assays. Genotypes of XPD Ile199Met, XPD Asp312Asn, and XPD Lys751Gln were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. The results indicate that the genotypes of XPD 751Lys/Gln and Gln/Gln were significantly associated with the expression of DNA damages (OR 2.21, P<0.05, 95% CI 1.01-5.13). An interesting observation is the reduction of DNA damage for workers with high VCM exposure and possessing the XPD Asp/Asn and Asn/Asn genotypes (OR 0.33, 95% CI 0.11-0.95). Polymorphisms of XPD may therefore be a major reason of genetic susceptibility in VCM-induced DNA damage and health consequences.