• BMB Reports
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• v.51 no.11
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Toxicological Research
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• v.21 no.1
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• pp.15-21
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• 2005

There is now a growing concern about the possible toxicity of heavy metals in cosmetics. Heavy metals can be used as cosmetic ingredients or may be present as low level impurities in some of the raw materials. Chromium derivatives are used as pigments in cosmetics. Chromium is essential and toxic trace elements. Chromium may cause skin allergy. However, the regulations related to cosmetic products give no limit values for Chromium. Hexavalent chromium is significantly more toxic than trivalent chromium. Hexavalent chromium may present a carcinogenic risk at high concentrations. Therefore, it is important to consider oxidation state of chromium when analyze chromium. The purpose of this study is to determine the concentrations of water-soluble trivalent and hexavalent chromium in samples of makeup products, and to assess the safety of cosmetics on the basis of animal sensitization tests using guinea pig. The present study of chromium in 48 makeup products of 12 manufacturers provides a basis for assessing safety of makeup products. Water-soluble hexavalent chromium was not detected in any product. Water-soluble trivalent chromium was detected in only 9 eye shadows out of 48 makeup products, and could not be quantified 3 out of 9 eye shadows. The highest level of water-soluble trivalent chromium was about 10 mg/kg in spite of 90,000 mg/kg of total chromium. The results of animal sensitization tests show that 200 mg/kg of trivalent chromium and 5 mg/kg of hexavalent chromium have no harmful effect. No cross-reaction among these metals was found. Accordingly, the concentrations of water-soluble chromium in makeup products seemed to be safe. The overall results indicate that chromium in cosmetics probably have no significant toxicological effects. However, It is necessary to set guidelines on the maximum permissible concentration of water-soluble chromium in cosmetics.

• Toxicological Research
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• v.31 no.3
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• pp.255-264
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• 2015

Heterocyclic amines (HCAs) and acrylamide are unintended hazardous substances generated by heating or processing of foods and are known as carcinogenic and mutagenic agents by the animal experiments. A simple method was established for a rapid and accurate determination of 12 types of HCAs (IQ, MeIQ, Glu-P-1, Glu-P-2, MeIQx, Trp-P-1, Trp-P-2, PhIP, $A{\alpha}C$, $MeA{\alpha}C$, Harman and Norharman) and acrylamide in three food matrices (non-fat liquid, non-fat solid and fat solid) by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In every sample, a mixture of internal standards including $IQ-d_3$, $MeIQx-d_3$, $PhIP-d_3$, $Trp-P-2-^{13}C_2-^{15}N$ and $MeA{\alpha}C-d_3$ was spiked for quantification of HCAs and $^{13}C_3$-acrylamide was also spiked for the analysis of acrylamide. HCAs and acrylamide in sample were extracted with acetonitrile and water, respectively, and then two solid-phase extraction cartridges, ChemElut: HLB for HCAs and Accucat: HLB for acrylamide, were used for efficiently removing interferences such as pigment, lipid, polar, nonpolar and ionic compounds. Established method was validated in terms of recovery, accuracy, precision, limit of detection, limit of quantitation, and linearity. This method showed good precision (RSD < 20%), accuracy (71.8~119.1%) and recovery (66.0~118.9%). The detection limits were < 3.1 ng/g for all analytes. The correlation coefficients for all the HCAs and acrylamide were > 0.995, showing excellent linearity. These methods for the detection of HCAs and acrylamide by LC-MS/MS were applied to real samples and were successfully used for quantitative monitoring in the total diet study and this can be applied to risk assessment in various food matrices.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2961-2966
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• 2012

Extremely low frequency electro magnetic fields (EMFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. An increased number of chromosomal alterations in peripheral lymphocytes are correlated with elevated incidence of cancer. The aim of the present study was to assess occupationally induced chromosomal damage in EMF workers exposed to low levels of radiation. We used conventional metaphase chromosome aberration (CA) analysis and the micronucleus (MN) assay as biological indicators of non ionizing radiation exposure. In the present study totally 70 subjects were selected including 50 exposed and 20 controls. Informed written consent was obtained from all participants and the study was performed in accordance with the Declaration of Helsinki and the approval of the local ethical committee. A higher degree of CA and MN was observed in exposed subjects compared to controls, the frequency of CA being significantly enhanced with long years of exposure (P<0.05). Moreover increase in CA and MN with age was noted in both exposed subjects and controls, but was significantly greater in the former. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers occupationally exposed to EMFs in electric transformer and distribution stations. In conclusion, our findings suggest that EMFs possess genotoxic capability, as measured by CA and MN assays; CA analysis appeared more sensitive than other cytogenetic end-points. It can be concluded that chronic occupational exposure to EMFs may lead to an increased risk of genetic damage among electrical workers.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1097-1102
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• 2016

Background: Liver fluke infection with Opisthorchis viverrini and its associated cholangiocarcinoma constitute a serious problem in Thailand. Healthy behavior can decrease infection, therefore, the investigation of knowledge, attitude, and practice is need required in high risk areas. Objective: This study aimed to investigate the behavior and perceptions regarding liver fluke. Materials and Methods: A cross-sectional descriptive study was conducted in Chum Phuang district of Nakhon Ratchasima province, Thailand during July to November 2015. A total 80 participants who had screened with verbal screening test, stool examination, and ultrasonography, were purposive selected and completed a pre-designed questionnaire (Kruder-Richardon-20=0.80, Cronbach's alpha coefficient=0.82 and 0.79). T-test, ANOVA, and Pearson correlation test were used for analyzed data. Results: The results reveal that O. viverrini infection was 1.25%, and 3 patients had a dilated bile ducts. The participants had a high knowledge, attitude, and practice regarding liver fluke. The education, occupation, and income, were statistical significant to attitude regarding liver fluke. Nurses and television were the main sources of information regarding liver fluke, with statistical significance(p-value <0.05). Knowledge was significantly associated with attitude and practice (p-value<0.05). Conclusions: Participants had good behavior regarding liver fluke. Improvement of knowledge and attitude is influenced to practical change regarding this carcinogenic fluke. In addition, nurse and television are the main information resources for key success in increasing people perception for disease prevention and control in this area.

• Journal of the Korean Chemical Society
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• v.61 no.2
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• pp.51-56
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• 2017

N-nitrosamines are the nitroso compounds which are produced by nitrosation reactions of the secondary amine and nitrite under acidic conditions. Approximately 300 species of N-nitrosamine have been tested for carcinogenicity in laboratory experiments, with 90% of them demonstrated carcinogenic effects different animal species, including higher primates. In 1978, IARC classified NDMA and NDEA as Group 2A, and NDPA, NDBA, NPIP, NPYR and NMOR as Group 2B. In this study, we established pretreatment and analytical method for N-nitrosamines (NDMA, NDEA, NMEA, NDPA, NDBA, NPIP, NPYR and NMOR) in human urine for biological monitoring of N-nitrosamines. The analytes were extracted using solid phase extraction (SPE), then quantitative analysis was performed by LC-(APCI)-MS/MS. The accuracies of the established method were between 85.8~108.7% and precisions were lower than 20%. The limit of detection (LOD) were between 0.0002 (NDBA) and 0.0793 (NDMA) ng/ml. The linearity obtained was satisfying for the 8 N-nitrosamines, with a coefficient of determination ($r^2$) higher than 0.999. The mean concentrations of N-nitrosamines in the urine were 2.645 mg/g creatinine for NDMA, 0.067 mg/g creatinine for NDEA, 0.009 mg/g creatinine for NMEA, 0.011 mg/g creatinine for NDBA, 0.271 mg/g creatinine for NPIP and 0.413 mg/g creatinine for NPYR. NDPA and NMOR were not detected. It can be used as a instrumental methodology for evaluation and risk assessment of human exposure to N-nitrosamines for the further research.

• Journal of environmental and Sanitary engineering
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• v.7 no.2
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• pp.95-110
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• 1992

Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.177-181
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• 2016

This cross-sectional descriptive and qualitative study was aimed to study the people participation and their approaches toward the human carcinogenic liver fluke, Opisthorchis viverrini, prevention and control in Ban Chaun sub-district administrative organization (BCSAO) and Bamnet Narong sub-district municipality (BNSM), Bamnet Narong district, Chaiyaphum Province, Thailand between June 2013 and February 2014. Participants were purposive selected, included chiefs of sub-district administrative organizations, sub-district municipalities, sub-district health promotion hospitals (SHPHs), heads of village, and a further sample was selected with a multi-stage random sampling for public health volunteers, and villagers. The pre-designed questionnaire contained items for individualized status and the participatory steps of sharing ideas, decision-making, and planning, procession, evaluation, and mutual benefit, for the project O. viverrini prevention and control (POPC). In-depth interviews were used for collection of need approaches to POPC. With 375 participants who completed the questionnaire, it was found that people had a high level regarding to participate in the POPC, particularly in the process stage ($\bar{X}=3.78$, S.D. = 0.56), but the lowest level was found in sharing ideas, decision making, and planning step ($\bar{X}=3.65$, S.D. = 0.63). By comparison, participant status and organization did not significantly differ with people participation. In each step, Ban Chaun sub-district had a high level of participation in the step of sharing ideas, decision making, and planning toward POPC, more than Bamnet Narong sub-district municipality (t=2.20, p=0.028). Approaches for POPC in Ban Chaun sub-district and Bamnet Narong sub-district municipality included requirements for budget support, annual campaigns for liver fluke prevention and control, campaign promotion, risk group observation, home visiting, community rules regarding reducing raw fish consumption in their communities, and a professional public health officer for working in their communities, BCSAO, BNSM, and SHPH, for O. viverrini prevention and control. This study indicates that people realize that eradication of the liver fluke needs a continuous people participation for O. viverrini prevention and control in their communities.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.32 no.4
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• pp.381-392
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• 2022

Objectives: Objective of this study is to review briefly exposure characteristics, monitoring instruments and threshold limit values for extremely low frequency-magnetic field (ELF-MF) methods. This study was undertaken through brief literature review. We performed a literature search in PubMed to identify ELF-MF studies conducted in workplaces. Initial search keywords such as 'extremely low frequency-magnetic field (ELF-MF)' and 'electromagnetic fields (EMF)' combined or singly. We limited our review to occupational rather than general nonworkplace environmental exposures. Methods: The contents we reviewed: key industry and occupations generating ELF-MF, several direct-reading instruments monitoring ELF-MF and threshold limit values (TLV) preventing health effects may be caused by the exposure to ELF-MF. Results: The industries related to the generation and supply of electricity, electrolytic installations, welding, and induction heating and more were regarded as high ELF-MF exposure industries. All jobs handling or employed performed in power cable lines, electrical wiring, and electrical equipment are found to be exposed to ELF-MF. Threshold or ceiling limit, 1,000 µT, is established to prevent acute effects of exposure to low-frequency EMFs on the nervous system: the direct stimulation of nerve and muscle tissues and the induction of retinal phosphenes. The International Agency for Research on Cancer (IARC) has classified ELF-MF as possibly carcinogenic to humans chiefly based on epidemiological studies on childhood leukemia. However, a causal relationship between magnetic fields and several types of cancer including childhood leukemia has not been established nor has any other long-term effects. Risk management using precautionary measures, has been initiated by the US and EU to prevent chronic health effects related to ELF-MF exposure in workplaces. Conclusion: This study recommends the implementation of various measures such as theestablishment of occupational exposure limit values for ELF-MF and precautionary principle to prevent potential chronic occupational health effects may be caused by ELF-MF in Korea.