• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 국제심포지움
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• pp.20-45
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• 2002

In this study, we demonstrated the in vitro and in vivo formation of carcinogen-lipid adduct and its correlation with DNA or protein adducts. The lipids from serum or hepatocyte membranes of Spragu-Dawley rats. human serum, and standard major lipids were in vitro reacted with benzo[a]pyrene(BP) and BP metabolites. 7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene(BPDE-I), an ultimate carcinogenic form of BP, was covalently bound to triglyceride(TG). BPDE-I-TG adducts isolated by thin-layer chromatography (TLC) were further detected by high performance liquid chromatography(HPLC). TGs, including triolein, tripalmitin and tristearin, showed positive reactions with BPDE-I. However, cholesterol, phospholipids(Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidyl-inositol and sphingomyelin) and nonesterified fatty acids(palmitic acid, oleic acid, linoleic acid and stearic acid) did not react with BPDE-I. In addition, other BP metabolites (BP-phenols and -diols) did not react with TG, which TG appeared to be the most reactive lipid yet studied with respect to its ability to form an adduct with BPDE-I. There was a clear-cut dose-respect to its ability to form an adduct with BPDE-I-lipid adduct in vitro between TG and [1,3-3H]BPDE-I. In an animal study, BPDE-I-TG was also formed in the serum of rats orally treated with BP(25 mg/rat). Also, obvious correlations between [3H]BP related-biomolecule adducts (DNA, protein) or lipid damage and the BPDE-I-TG adduct were obtained in various tissues of mice i.p. treated with [3H]BP. These data suggest that TG can form an adduct with BPDE-I, as do other macromolecules (DNA, RNA, and protein). Therefore, a carcinogen-lipid adduct would be a useful biomarker for chemical carcinogenesis research and cancer risk assessment.

• 한국가금학회:학술대회논문집
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• 한국가금학회 2005년도 제22차 정기총회 및 학술발표회
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• pp.17-30
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• 2005

Lycopene is the red-coloured carotenoid predominantly found in tomato fruit and one of the major carotenoids in the diets of North American and Europeans. Interest in lycopene is growing rapidly following the recent publication of its effects as a natural antioxidant and prevention of cardiovascular disease and cancers. Lycopene, a polyene hydrocarbon carotenoid haying 13 double bond, of which 11 are conjugated double bonds in a linear array exhibits a strong antioxidant property almost twice as strong as that of ${\beta}$-carotene. Lycopene has been shown in recent epidemiological and experimental studies to protect against oxidative damage of DNA which plays an important part in development of various cancer. Lycopene also contribute towards reducing the risk of cardiovascular diseases by preventing oxidation of low-density lipoprotein(LDL) cholesterol. This review summarize our knowledge and the current understanding of lycopene in human health as well as the results of experiments we conducted. We conducted experiments for investigating the effects of antioxidant in broiler and the possibilities of production of high quality eggs containing lycopene by the dietary lycopene supplementation with synthetic lycopene or tomato paste. The results shows that thiobarbituric acid reaction substances(TBARS) values in process of LDL oxidation in blood serum of broiler were significantly decreased by dietary lycopene and tomato paste. The dietary lycopene supplementation resulted in improved egg yolk color and in decreased the malondialdehyde (MDA) of egg yolk after 4 wk of storage at room temperature significantly(P<0.05). The dietary tomato paste was more effective in the MDA reduction compared to the lycopene(P<0.05). The contents of lycopene in egg yolk of the lycopene supplementation groups were significantly higher than those of the control group.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1315-1319
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• 2015

The fact that long-term use of proton pump inhibitors (PPIs) aggravates corpus atrophic gastritis in patients with Helicobacter pylori infection has been proven clinically and experimentally. Corpus atrophic gastritis is a known risk factor for gastric cancer. Therefore, gastric neoplasia might be associated with the long-term use of PPIs. One of the causes of worsening corpus atrophic gastritis, leading to the development of adenocarcinoma, might be bacterial overgrowth under conditions of hypochlorhydria. The production of potentially carcinogenic N-nitrosocompounds by nitrosating organisms under conditions of hypochlorhydria might be associated with carcinogenesis. Interactions between bile acids, pH, and H. pylori might also contribute to carcinogenicity, especially in patients with gastro-esophageal reflux disease (GERD). The concentration of soluble bile acids, which have bactericidal or chemorepellent properties toward H. pylori, in gastric contents is considerably higher in patients undergoing continuous PPI therapy than in healthy individuals with normal acid production. Under these circumstances, H. pylori might colonize the stomach body rather than the pyloric antrum. Hypergastrinemia induced by PPI administration might promote the development of gastric cancer. Because the main cause of corpus atrophic gastritis is H. pylori infection, and not PPI administration, H. pylori infection should be eradicated before starting long-term PPI therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1151-1157
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• 2015

Human papillomavirus (HPV) is responsible for one of the most frequent sexually transmitted infections. The first phylogenetic analysis was based on a LCR region fragment. Nowadays, 4 variants are known: African (Af-1, Af-2), Asian-American (AA) and European (E). However the existence of sub-lineages of the European variant havs been proposed, specific mutations in the E6 and LCR sequences being possibly related to persistent viral infections. The aim of this study was a phylogenetic study of HPV16 sequences of endocervical samples from C${\acute{o}}$rdoba, in order to detect the circulating lineages and analyze the presence of mutations that could be correlated with malignant disease. The phylogenetic analysis determined that 86% of the samples belonged to the E variant, 7% to AF-1 and the remaining 7% to AF-2. The most frequent mutation in LCR sequences was G7521A, in 80% of the analyzed samples; it affects the binding site of a transcription factor that could contribute to carcinogenesis. In the E6 sequences, the most common mutation was T350G (L83V), detected in 67% of the samples, associated with increased risk of persistent infection. The high detection rate of the European lineage correlated with patterns of human migration. This study emphasizes the importance of recognizing circulating lineages, as well as the detection of mutations associated with high-grade neoplastic lesions that could be correlated to the development of carcinogenic lesions.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.12.1-12.8
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• 2012

Objectives: The aim of this study was to identify the health and environmental risk factors of air contaminants that influence environmental and respiratory diseases in Gyeongju, Pohang and Ulsan in South Korea, with a focus on volatile organic compounds (VOCs). Methods: Samples were collected by instantaneous negative pressure by opening the injection valve in the canister at a fixed height of 1 to 1.5 m. The sample that was condensed in $-150^{\circ}C$ was heated to $180^{\circ}C$ in sample pre-concentration trap using a 6-port switching valve and it was injected to a gas chromatography column. The injection quantity of samples was precisely controlled using an electronic flow controller equipped in the gas chromatography-mass spectrometer. Results: The quantity of the VOC emissions in the industrial area was 1.5 to 2 times higher than that in the non-industrial area. With regards to the aromatic hydrocarbons, toluene was detected at the highest level of 22.01 ppb in Ulsan, and chloroform was the halogenated hydrocarbons with the highest level of 10.19 ppb in Pohang. The emission of toluene was shown to be very important, as it accounted for more than 30% of the total aromatic hydrocarbon concentration. Conclusions: It was considered that benzene in terms of the cancer-causing grade standard, toluene in terms of the emission quantity, and chloroform and styrene in terms of their grades and emission quantities should be selected for priority measurement substances.

• 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.

• 한국축산식품학회지
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• 제41권2호
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• pp.173-184
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• 2021

Clean labeling is emerging as an important issue in the food industry, particularly for meat products that contain many food additives. Among synthetic additives, nitrite is the most important additive in the meat processing industry and is related to the development of cured color and flavor, inhibition of oxidation, and control of microbial growth in processed meat products. As an alternative to synthetic nitrite, preconverted nitrite from natural microorganisms has been investigated, and the applications of pre-converted nitrite have been reported. Natural nitrate sources mainly include fruits and vegetables with high nitrate content. Celery juice or powder form have been used widely in various studies. Many types of commercial starter cultures have been developed. S. carnosus is used as a critical nitrate reducing microorganism and lactic acid bacteria or other Staphylococcus species also were used. Pre-converted nitrite has also been compared with synthetic nitrite and studies have been aimed at improving utilization by exploiting the strengths (positive consumer attitude and decreased residual nitrite content) and limiting the weaknesses (remained carcinogenic risk) of pre-converted nitrite. Moreover, as concerns regarding the use of synthetic nitrites increased, research was conducted to meet consumer demands for the use of natural nitrite from raw materials. In this report, we review and discuss various studies in which synthetic nitrite was replaced with natural materials and evaluate pre-converted nitrite technology as a natural curing approach from a clean label perspective in the manufacturing of processed meat products.

• 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.

• Korean Journal of Radiology
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• 제21권1호
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• pp.68-76
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• 2020

Objective: To survey care providers' willingness to use 2-mSv computed tomography (CT) in their usual practice for adolescents and young adults with suspected appendicitis. Materials and Methods: An ethical committee approved this prospective study. We introduced 2-mSv CT in 20 hospitals through a pragmatic clinical trial. At the final phase of the trial, we invited 698 potentially-involved care providers in the survey regarding their willingness to use 2-mSv CT. Multivariable logistic regression analyses were performed to identify factors associated with willingness. Nine months after the completion of the trial patient recruitment, we surveyed whether the hospitals were using 2-mSv CT in usual practice. Results: The analyses included responses from 579 participants (203 attendings and 376 trainees; 221 radiologists, 196 emergency physicians, and 162 surgeons). Regarding the willingness to immediately change their standard practice to 2-mSv CT, 158 (27.3%), 375 (64.8%), and 46 (7.9%) participants responded as "yes" (consistently), "partly" (selectively), and "no", respectively. Willingness varied considerably across the hospitals, but only slightly across the participants' departments or job titles. Willingness was significantly associated with attendings (p = 0.004), intention to maintain the dedicated appendiceal CT protocol (p < 0.001), belief in compelling evidence on the carcinogenic risk of conventional-dose CT radiation (p = 0.028), and hospitals having more than 1000 beds (p = 0.031). Fourteen of the 20 hospitals kept using 2-mSv appendiceal CT in usual practice after the trial. Conclusion: Despite the extensive efforts over the years of this clinical trial, many care providers were willing to use 2-mSv CT selectively or not willing to use.

• 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.