• Maxillofacial Plastic and Reconstructive Surgery
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• 제32권3호
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• pp.218-228
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• 2010

발암물질로 알려진 Hydroquinone (HQ)은 치과용 합성수지를 구성하는 중요한 성분으로서 지금까지 치과용 재료영역에서 널리 사용되고 있으며 구강 내에서 HQ의 유출이 일어나는 것으로 확인 되었다. 따라서 구강암의 기원이 되는 인체상피세포의 발암화에 HQ가 미치는 영향을 평가하였다. HQ에 의한 인체세포 독성을 평가하기위해 LDH assay를 실시하고 세포 독성이 높지 않은 용량을 실험 용량으로 설정하였다. 인체 세포의 발암화를 평가하기 위해 세포 발암화 지표로서 cell saturation density, soft-agar colony formation 및 cell aggregation의 분석을 사용한 결과 고용량인 50 ${\mu}M$을 제외한 모든 용량에서 발암화 지표의 변화를 나타내지 않아 HQ의 발암력은 매우 낮은 것으로 추정된다. 그러나 발암촉진제인 TPA와 함께 투여 시 발암력의 증가를 보여 주변 환경의 여건에 따라 발암력이 증가할 수 있음을 입증하였다. HQ를 노출 후 세포사멸화를 측정하기 위해 DNA fragmentation변화를 분석한 결과 10 ${\mu}M$부터 50 ${\mu}M$까지 노출 시간 의존형의 증가를 나타내었으며 50 ${\mu}M$과 같은 고용량 농도에서는 노출시간 의존적 세포사멸 효과를 보였다. 따라서 세포 발암화를 일으킨 용량에서 세포사멸도 함께 일어나 HQ에 의한 발암화에 세포사멸이 관여함을 보였다. HQ는 ROS를 생성하였으며 Trolox, NAC와 같은 항산화물에 의한 ROS의 차단 효과와 BSO와 같은 GSH 고갈 유발 물질에 따른 ROS의 급격한 증가는 HQ가 인체세포에서 ROS를 효율적으로 생성함을 입증하는 결과이다. 세포간의 신호전달기작 조절에 중요한 역할을 하는 효소인 protein kinase C (PKC)를 immunoblot으로 분석한 결과 PKC-${\alpha}$의 활성이 증가 된 반면 PKC-${\beta}II$의 영향은 나타나지 않았다. 따라서 특정 이성질체에 대한 특이적인 효소반응이 발암화에 관여할 것으로 추정된다. 본 연구결과 치과용 합성수지 구성성분인 HQ 유출에 따른 인체상피세포의 발암성은 매우 낮은 것으로 추정되나 발암촉진제 등과의 상호작용에 의한 발암성 증가는 HQ의 구강암 발생 평가에 고려되어야 할 사항이다. 따라서 본 연구는 구강암의 예방을 위한 과학적인 접근 방법 및 기반 자료를 제시하였고 치과용 합성수지사용의 적정성에 대한 과학적인 판단을 할 수 있는 근거를 제공 하였다. 또한 본 연구 결과는 새로운 치과용 합성수지 개발의 필요성 및 개선방향을 제시 할 수 있는 근거로 활용될 수 있을 것으로 사료된다.

• 한국환경성돌연변이발암원학회지
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• 제26권1호
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• pp.12-19
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• 2006

Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.209-215
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• 2005

Recently, a large number of clinical experiments have shown that exposure of organic pollutants lead to various cancers through the abnormal cell growth. Environmental pollutants, such as 2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs), are carcinogen and are known to cause the cognitive disability and motor dysfunction in the developing of brain. The effects of these pollutants on neurodevelopmental disorder is well established, but the underlying mechanism(s) and similarity of gene expression profiles in human brain tumors with organic pollutants still remain unclear. In this study, we first examined the gene expression profiles in glioblastomas compared with meningioma that are kinds of primary human brain tumor by using human cDNA microarray. The results of cDNA microarray analysis revealed that 26 genes were upregulated (Z-ratio>2.0) and 14 genes were downregulated (Z-ratio<-2.0) in glioblastoma compared with meningioma. From the altered gene patterns, mitogen-activated protein kinase (MAPK) signaling related genes, such as MAP2K3, MAP3K11 and jun activated domain binding protein, and transcription factors, such as UTF2 and TF12, were upregulated in glioblastoma. Also, we tried to investigate the relation between important genes up- and down-regulated in giloblastoma and various organic pollutants. Therefore, the identification of changes in the patterns of gene expression may provide a better understanding of the molecular mechanisms involved in human primary brain tumors and of the relation between gene expression profiles and organic pollutants in brain tissue.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.187-191
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• 2003

In this study, biomonitoring methods were developed to measure BTEXs exposure level in the air, metabolites of benzene and toluene in human urine, individual susceptibility markers in human blood for evaluation of the health effects about environmental pollution. We have also performed a small-scaled molecular epidemiology study on residents in Chuncheon and workers in workplace for these method applications. The workers in workplace were surveyed as study areas, and the residents in Chuncheon which is in the suburban area were surveyed as comparative areas in this study. Actually, 31 workers in as target group and 33 residences in as control group this epidemiological study. The results obtained from this study were as follows: 1. Benzene is a well-known carcinogen, it's median concentrations were 0.00024∼0.02057ppm at suburban area and 0.002∼00.654ppm at work place, These benzene concentrations were not exceed the OSHA(Occupational Safety and Health Administration) threshold benzene level of 1ppm in the states. 2. Metabolites product of benzene(t,t-Muconic Acid) and toluene(Hippuric Acid) were not significant both in suburban and workplace area. The median concentration of t,t-MA and HA were 0.0122, 1.44277g/g creatinine, respectively. 3. In the case of individual susceptibility markers as CYPlAl, 41.8% of them has homozygous wild type(W) and who has heterozygous variant type(H) was 35.4% and 22.8% of homozygous variant type(M) genetic type. In the case of CYP2E1, 62.82% of them has homozygous wild type(D) type, 34.62% of each has heterozygous variant type (DC) and 2.56% of them has homozygous variant type (CC). Who doesn't have GSTM1 gene was 46.25% and who has GSTM1 gene was 53.75％. Who doesn't have GSTT1 gene was 40.0％ in study groups and who has GSTT1 gene was 60.0%. Who has W genetic type, which is homozygous wild type of GSTP1, was 69.18% and H genetic type, which is heterozygous variant type was 28.4%. M genetic type which is homozygous variant type was 2.4%. 4. Concentration differences of metabolites such as t,t-MA and HA in urine, which is generated by individual susceptibility marker of GSTM1, GSTT1, GSTP1 gene of Phase I and CYP1A1, CYP2E1 gene of Phase II, was examined. As a result, GSTP1 and GSTM1 indicate slight differences depend on the amount of metabolites in urine, it was not statistically significant.

• Journal of Ginseng Research
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• 제39권3호
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• pp.265-273
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• 2015

Background: Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticancer and antioxidative potential of Panax ginseng against chemical-induced skin carcinogenesis in mammals. Methods: Skin tumors were induced in Swiss albino mice by a single topical application of 7,12-dimethylbenz(a)anthracene ($100{\mu}g/100{\mu}L$ acetone) and, 2 wks later, promoted by repeated applications of croton oil (thrice in a wk in 1% acetone) till the end of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of 25 mg/kg body weight/d was orally administered at the periinitiation, postinitiation, and peri-post-initiation stages. Results: Ginseng root extract treatment caused a significant reduction in tumor incidence, cumulative number of tumors, tumor yield, and tumor burden, as compared to the 7,12-dimethylbenz(a)anthracene-croton oil-treated control group. Further, biochemical assays revealed a significant enhancement in the levels of reduced glutathione, superoxide dismutase, catalase, vitamin C, and total proteins but a significant reduction in lipid peroxidation levels in both the liver and skin with ginseng root extract treatment, as compared to carcinogen-treated control group. Conclusion: These results suggest that P. ginseng has the potential to become a pivotal chemopreventive agent that can reduce cancer in mammals.

• 한국산업보건학회지
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• 제25권4호
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• pp.446-464
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• 2015

Objectives: This study was conducted to evaluate the task-specific hazards of chemicals used by nail technicians in Daegu Metropolitan City. Materials: A total of 30 nail shops located in Daegu City were surveyed to investigate the major tasks and practices performed by nail technicians and the ingredients listed in nail care products used in shops. We also collected instructions for use and material safety data sheets(MSDSs) of nail care products and compared CAS Nos. of ingredients with the lists of chemicals regulated by the Industrial Safety and Health Act(ISHA) and Chemical Substances Control Act(CSCA). Results: A total of 125 chemical ingredients were found in 468 nail care products used at the 30 nail shops. The most frequently found ingredients were ethyl acetate(72%), followed by n-butyl acetate(71.8%), isopropanol(56%), benzophenone(51.1%), nitrocellulose(46.4%) and ethanol(45.3%). Comparing six tasks, the task of manicuring used the most products at 222 products containing 91 ingredients. Among the 125 ingredients, there are 31 chemicals with occupational exposure limits(OEL) designated by the Ministry of Employment and Labor(MoEL), eight categorized as carcinogens, one mutagen and two reproductive toxic chemicals. In terms of carcinogens, formaldehyde was identified as the only confirmed human carcinogen(1A). We found that there was one chemical with a permissible limit, one special management substance, 18 workplace monitoring substances and ten special health diagnosis substances regulated by ISHA. For CSCA, nine poisonous substances, six substances requiring preparation for accidents and one restricted substance were identified. Conclusions: Based on these findings, formaldehyde was identified as one of the chemicals that should most strictly be controlled for the protection of the health of nail technicians and customers. At the same time, it is necessary to distribute materials with detailed hazardous information of nail care products for nail shop technicians.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2004년도 춘계학술발표대회
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• pp.222-222
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• 2004

Superoxide dismutases are key antioxidant enzymes in metabolism of reactive oxygen species. Three different isoforms of SOD exist in mammals. The extracellular SOD (EC-SOD) is the most recently discovered SOD family member. This isoform is a copper- and zinc-containing enzyme like Cu/Zn-SOD and a homotetrameric glycoprotein with a molecular weight of about 165 kDa in mouse. (omitted)

• Toxicological Research
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• 제29권2호
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• pp.137-142
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• 2013

Arsenic (As) is a well-known human carcinogen and its dietary exposure has been found to be the major route of entry into general population. This study was performed to assess the body levels of As and their associated factors in Korean adults by analyzing total As in urine. Urine and blood samples were collected from 580 adults aged 20 years and older, who had not been exposed to As occupationally. Demographic information was collected with the help of a standard questionnaire, including age, smoking, alcohol intake, job profiles, and diet consumed in the last 24 hrs of the study. Total As, sum of As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), in urine was determined using atomic absorption spectrometer involving hydride generation method. The geometric mean concentration of total As in urine was $7.10{\mu}g/L$. Urine As was significantly higher in men ($7.63{\mu}g/L$) than in women ($6.75{\mu}g/L$). Age, smoking, alcohol consumption, and job profiles of study subjects did not significantly affect the concentration of As in urine. No significant relationship was observed between body mass index (BMI), Fe, and total cholesterol in serum and urinary As. Urine As level was positively correlated with seaweeds, fishes & shellfishes, and grain intake. A negative correlation between urinary As level and HDL-cholesterol in serum and meat intake was observed. Overall, these results suggest that urinary As concentration could be affected by seafood consumption. Therefore, people who frequently consume seafood and grain need to be monitored for chronic dietary As exposure.

• 한국산업보건학회지
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• 제18권2호
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• pp.99-107
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• 2008

We quantified the human carcinogenic metals (chromium, nickel) in fumes from flux cored arc welding using stainless steel (FCAW/SS) wires. Zinc and calcium were also quantified because of their possibility of zinc chromate and calcium chromate, respectively. Welding was performed in an American Welding Society standard fume collection chamber. Insoluble and soluble forms of metals were analyzed by ISO 15202 method. Total chromium (insoluble+soluble) content and total nickel content were lower in FCAW/SS fumes (4.65%, 1.05%, respectively)than in stainless steel content (ca. 18%, 8%,respectively). Insoluble fraction in total chromium was 79.8 (range 64.5~95.1)% and 94.4(range 90.1~98.1)% in total nickel. Atomic emission spectroscopy used in this study does not differentiate the chromium valence status while ACGIH defines its carcinogenicity according to the valence status. From this study and previous study, we estimated the hexavalent chromium content in FCAW/SS was 0.2~1.1% and about 85% of them was soluble. The content of zinc and calcium, which can be existed as chromate forms, was low (0.02 %, 0.04% respectively) in FCAW/SS. Exposure assessment for zinc chromate and calcium chromate is possible because chromium in both compounds is used as a surrogate even though it is not well known that what compounds of zinc and calcium are formed in welding fume.

• Parasites, Hosts and Diseases
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• 제55권1호
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• pp.21-29
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• 2017

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs.