• 한국식품위생안전성학회지
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• 제25권2호
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• pp.148-152
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• 2010

우리나라 유아들이 비소에 노출된 경우의 인체위해성에 대한 상관관계 연구가 미비한 실정이다. 본 연구는 우리나라 광신인근 지역에서 생산된 백미의 섭취를 통한 비소의 노출을 유아기(1-6세)와 타 연령군으로 나누어 평가하고 해당 연령군의 인체위해성 평가를 확률적 접근법을 이용해 실시하였다. 우리나라 광산인근 지역에서 생산된 백미 섭취를 통한 D아기의 비소 노출량은 체중을 기준으로 했을 때 타 연령군에 비해 높게 나타났다. 피부암에 대한 초과발암위해의 경우 1-2세 군과 3-6세 군의 50% percentile값이 각각 만명 당 1.76명과 3.16명으로 나타났다. 어린이와 같은 아만성기간 동안의 비소 노출에 대한 비발암 기준 참고치(0.005 mg/lg/day)를 적용한 결과 비발암위해도의 평균값 뿐 아니라 고섭취군을 나타내는 95% percentile 값 또한 규제수치인 1.0 이하로 나타났다.

• Toxicological Research
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• 제30권4호
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• pp.261-266
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• 2014

Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have been implicated in cancer development and progression. However, the effects of PAHs on carcinogenesis are still poorly understood. Here, we characterized a mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non-tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the expression level of mRNA and proteins, respectively. To determine functionality, cell motility was assessed in vitro using a transwell migration assay. Both mRNA and protein levels of E-cadherin were significantly decreased in 1MEA cells in comparison with BNL cells. While the expression levels of mesenchymal markers and related transcription factors were enhanced in 1MEA cells, which could lead to increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3-MC reduced the level of the adhesion molecule and epithelial marker E-cadherin and increased reciprocally the level of the mesenchymal marker vimentin in a dose-dependent manner. Taken together, these results indicate that the process of epithelial-mesenchymal transition (EMT) may be activated during premalignant transformation induced by 3-MC. A mechanism study to elucidate the relation between 3-MC exposure and EMT is underway in our laboratory.

• 한국환경성돌연변이발암원학회지
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• 제23권2호
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• pp.56-62
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• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• 한국토양비료학회지
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• 제42권1호
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• pp.53-57
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• 2009

휴폐광산 인근 주민에 대한 위해영향을 평가하는데 있어서 벼 품종에 따른 변이를 파악하기 위하여 농경지 토양 및 쌀의 비소, 카드뮴, 구리 및 납의 함량을 분석하였다. 중금속 오염농경지에서 조사된 잠재적인 인체노출 경로로서 오염된 농경지 및 쌀을 통한 경구섭취 및 피부접촉을 통한 품종간 일일평균 인체노출량(ADD)을 산정하였다. 비발암성 위해도 평가로 노출경로별 중금속의 위험비율인 HQ 지수와 모든 노출경로를 총합한 중금속의 위험지수인 HI 값을 US-EPA D/B를 활용하였다. 벼 품종간 HI 지수는 23.6~34.3으로 전품종에서 높은 잠재적 위해성으로 평가되었는데 DA 품종이 가장 낮은 반면 TB 품종이 가장 높은 HI 값을 보였다. 쌀 소비에 따른 비소의 발암성 위해도 평가는 품종간 2.0E-03~3.5E-03을 보여 미국 EPA에서 정한 위해성 기준인 만명 중 한명 이상으로 높게 나타났다. 발암성 위해도에 대한 품종간 비교에서 DA 품종이 가장 낮은 반면 TB 품종이 가장 높은 HI 값을 보였다. 이러한 결과는 위해성 평가가 중금속 오염에 안전한 품종을 선발하는데 유용한 도구로서 활용할 수 있음을 보여준다.

• Asian-Australasian Journal of Animal Sciences
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• 제14권3호
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• pp.402-413
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• 2001

Food safety is a term broadly applied to food quality that may adversely affect human health. These include zoonotic diseases and acute and chronic effects of ingesting natural and human-made xenobiotics. There are two major areas of concern over the presence of residues of antibiotics in animal-derived foodstuffs with regard to human health. The first is allergic reactions. Some antibiotics, such as penicillins can evoke allergic reactions even though small amounts of them are ingested or exposed by parenteral routes. The second is development of antibiotic resistance in gut bacteria of human. Recently multi-resistant pneumococcal, glycopeptide-resistant enterococci and gram negative bacteria with extended-spectrum $\beta$-lactamases have spread all over the world, and are now a serious therapeutic problem in human. Although it is evident that drugs are required in the efficient production of meat, milk and eggs, their indiscriminate use should never be substituted for hygienic management of farm. Drug should be used only when they are required. In addition to veterinary drugs, environmental contaminants that were contaminated in feed, water and air can make residues in animal products. Mycotoxins, heavy metals, pesticides, herbicides and other chemicals derived from industries can be harmful both to animal and human health. Most of organic contaminants, such as dioxin, PCBs and DDT, and metals are persistent in environment and biological organisms and can be accumulated in fat and hard tissues. Some of them are suspected to have endocrine disrupting, carcinogenic, teratogenic, immunodepressive and nervous effects. The governmental agencies concerned make efforts to prevent residue problems; approval of drugs including withdrawal times of each preparation of drugs, establishment of tolerances, guidelines regarding drug use and sanitation enforcement of livestock products. National residue program is conducted to audit the status of the chemical residues in foods. Recently HACCP has been introduced to promote food safety from farm to table by reducing hazardous biological, chemical and physical factors. Animal Production Food Safety Program, Quality Assurance Programs, Food Animal Residue Avoidance Databank are para- or non-governmental activities ensuring food safety. This topic will cover classification and usage or sources of chemical residues, their adverse effects, and chemical residue status of some countries. Issues are expanded to residue detection methodologies, toxicological and pharmacokinetic backgrounds of MRL and withdrawal time establishments, and the importance of non-governmental activities with regard to reducing chemical residues in food.

• Toxicological Research
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• 제31권3호
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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.

• 한국지하수토양환경학회지:지하수토양환경
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• 제12권4호
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• pp.25-31
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• 2007

물질 간 상호작용이 위해도에 많은 영향을 미칠 수 있다는 것은 널리 알려져 있지만 이를 위해성평가에 적용할 수 있는 방안은 아직 미미한 실정이다. 본 연구에서는 p-xylene이 토양 내에 존재할 때, 대수층으로의 이동성이 극히 제한적인 benz[a]anthracene (BaA)의 지하수로의 이동성 증가를 확인하고 그 증가된 위해도를 산정하기 위하여, 지하 환경을 모사한 셀을 제작하여 실험을 수행하였으며, 이를 해석하는 간단한 물질이동 모델을 개발하였다. 셀 실험 결과 BaA의 이동성은, BaA와 p-xylene이 혼합물질로 동시에 존재하는 경우에, BaA만으로 오염되어 있는 경우보다 월등히 높았다. 후자의 경우는 강우에 의한 이동이 주요 이동기작이었으며 그 정도는 아주 미미하였다. Defined Time Steps (DTS)을 이용하여 개발된 오염물질 이동모델은 두 물질 모두 실험결과와 유사한 경향을 보이며 변하는 것을 확인하였으나, 더욱 정확한 예측을 위하여 모델의 수정, 보완작업이 계속되고 있으며 이는 다음 연구의 주제가 될 것이다. 실험실 규모의 셀 실험의 경우 모세관대가 물질이동에 중요한 역할을 하기 때문에 실험실 규모의 시뮬레이션에서는 모세관대 모듈을 적용하는 것이 보다 적합한 것으로 나타났다. 현장규모 오염에서의 모델링 결과를 토대로 위해도를 산정하고 비교한 결과, 지하수 섭취를 통한 BaA의 발암위해도는 NAPL이 존재할 때, 존재하지 않을 때보다, 약 15${\sim}$87배 크게 계산되었다. NAPL이 존재하지 않는 경우 BaA의 지중 이동속도는 매우 느리며, 실제 오염현장의 경우 이동 과정에서 물질분해가 일어나므로 NAPL의 존재 여부에 따른 실제 위해도 차이는 더 크게 발생할 것으로 예상된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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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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• 제55권3호
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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.