• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10937-10941
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• 2015

Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$=166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk.

• Journal of Preventive Medicine and Public Health
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• 제28권2호
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• pp.511-525
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• 1995

크롬염 안료제조공장 근로자를 대상으로 크롬 폭로와 말초혈액 림프구의 8-OH-dG 농도의 상관성을 직접 관찰함으로써 크롬의 암 발생기전에 산소유리기(oxygen free radical)가 관여하는지 여부와 크롬폭로에 따라 자매염색분체교환 빈도가 증가하는지를 밝힐 목적으로 본 연구를 수행하였다. 안료공장에 1년 이상 근무한 근로자 38명을 대상으로 설문지를 통하여 근무기간, 연령, 성, 크롬 폭로와 관련된 자각적 증상 등을 조사하였으며, 이들의 크롬 폭로 수준을 평가할 수 있는 생물학적 지표로서 혈중 및 크레아티닌 보정 요중 크롬 농도를 측정하였다. 크롬에 의한 생물학적 영향지표로서 말초혈액 림프구로 부터 dG에 대한 8-OH-dG의 몰 농도비를 측정하였으며, 분열 중기의 세포 30개를 관찰하여 세포당 자매염색분체교환 빈도를 계수하여 염색체 46개당 평균 자매 염색분체교환 빈도로 환산하였다. 분석결과 현재 크롬 폭로 수준을 판단하는 생물학적지표로 가장 많이 사용되는 크레아티닌 보정 요중 크롬 농도와 림프구에서의 dG에 대한 8-OH-dG의 물 농도비는 유의한 상관관계(r=0.47, p<0.01)를 보이는 것으로 분석되었으며, 현재의 흡연수준을 보정하고 분석한 결과에서는 상관계수가 증가하는 결과(r=0.62, p<0.05)를 나타내었다. 한편 자매염색분체교환 빈도와 크롬 폭로수준간에는 유의한 상관관계가 관찰되지 않았다. 이러한 결과는 크롬의 발암성에 DNA 부가체(adduct)의 형성이 중요한 기전일 수 있다는 기존의 연구결과와 일치하며, 따라서 8-OH-dG는 크롬에 의한 발암성을 예측할 수 있는 생물학적 영향지표로서 활용될 수 있음을 시사한다고 할 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7105-7112
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• 2014

In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) andTNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.

• Korean Journal of Acupuncture
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• 제41권2호
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

• 생명과학회지
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• 제20권4호
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• pp.618-622
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• 2010

본 연구는 비소에 대한 만성노출이 의심되는 일부 폐금속광산 주변 지역 주민 중 여성들을 대상으로 요중 비소 농도와 산화적 유전자 손상지표인 요중 8-hydroxydeoxyguanosine (8-OHdG) 농도와의 관련성을 평가하기 위해 시행되었다. 충청북도에 위치한 두 폐금속광산 지역 주민 중 여성 165명을 대상으로 요중 비소농도와 요중 8-OHdG의 농도를 측정하고 SPSS 12.0 통계프로그램을 이용하여 분석하였다. 조사 대상자들의 요중 비소농도는 기하평균이 $5.65\;{\mu}g/g$ creatinine으로 나타났으며 요중 비소와 8-OHdG 농도와의 관련성 분석에서는 상관계수 0.399 (p<0.001)의 유의한 상관성을 보였다. 이러한 관련성은 비소노출 농도가 낮은 경우가 노출농도가 높은 경우에 비해 상대적으로 높은 것으로 나타났다. 본 연구의 결과는 요중 8-OHdG 농도가 저농도의 비소에 만성적으로 노출된 여성에서 산화적 유전자 손상을 평가하는 좋은 지표가 될 수 있음을 시사한다.

• 생물정신의학
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• 제24권3호
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• pp.142-148
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• 2017

Objectives The ratio of second to fourth digit length (2D : 4D) could be a potential epigenetic marker of sexual dimorphism reflecting prenatal testosterone exposure. Testosterone is known to affect the development of the brain through an epigenetic mechanism. The purpose of this study was to investigate the effects of exposure to fetal testosterone on the metabolic syndrome based on 2D : 4D of schizophrenia patients and the relationship with the age of onset of schizophrenia. Methods A total of 214 schizophrenia patients participated in this study. The participant's physical and blood tests were performed according to the American National Cholesterol Education Program's Third Amendment of the Metabolic Syndrome Diagnostic Criteria, and the 2D : 4D was measured by the method designed by McFadden. Data were statistically analyzed by t-test, Pearson's correlation analysis and multiple regression model analysis. Results 2D : 4D was significantly higher in female than male in both hands, and there was a statistically significant negative correlation between 2D : 4D and the age of onset of schizophrenia in male. However, 2D : 4D did not show statistically significant correlation with metabolic factors. Conclusions Fetal testosterone suggests the possibility of affecting the age of onset of schizophrenia through the epigenetic mechanism, but there is no clear relationship with metabolic factors.

• 한국환경보건학회지
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• 제37권6호
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• pp.450-459
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• 2011

Objectives: Biomarkers in urine are important in assessing exposures to environmental or occupational chemicals and for evaluateing renal function by exposure from these chemicals. Spot urine samples are needed to adjust the concentration of these biomarkers for variations in urine dilution. This study was conducted to evaluate the suitability of adjusting the urinary concentration of cadmium (uCd) and arsenic (uAs) by specific gravity (SG) and urine creatinine (uCr). Methods: We measured the concentrations of blood cadmium (bCd), uCd, uAs, uCr, SG and N-acetyl-${\beta}$-D-glucosaminidase (NAG) activity, which is a sensitive marker of tubular damage by low dose Cd exposure, in spot urine samples collected from 536 individuals. The value of uCd, uAs and NAG were adjusted by SG and uCr. Results: The uCr levels were affected by gender (p < 0.01) and muscle mass (p < 0.01), while SG levels were affected by gender (p < 0.05). Unadjusted uCd and uAs were correlated with SG (uCd: r = 0.365, p < 0.01; uAs: r = 0.488, p < 0.01), uCr (uCd: r = 0.399, p < 0.01; uAs: r = 0.484, p < 0.01). uCd and uAs adjusted by SG were still correlated with SG (uCd: r = 0.360, p < 0.01, uAs: r = 0.483, p < 0.01). uCd and uAs adjusted by uCr and modified uCr ($M_{Cr}$) led to a significant negative correlation with uCr (uCd: r = -0.367, p < 0.01; uAs: r = -0.319, p < 0.01) and $M_{Cr}$ (uCd: r = -0.292, p < 0.01; uAs: r = -0.206, p < 0.01). However, uCd and uAs adjusted by conventional SG ($C_{SG}$) were disappeared from these urinary dilution effects (uCd: r = -0.081; uAs: r = 0.077). Conclusions: $C_{SG}$ adjustment appears to be more appropriate for variations in cadmium and arsenic in spot urine.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2699-2705
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• 2014

This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.

• 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.

• Applied Microscopy
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• 제37권1호
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• pp.1-10
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• 2007

MCT 유발 간독성 흰쥐에 해독정기탕의 투여가 시간경과에 따른 간세포의 항산화효소 활성변화, 세포사멸 억제와 간의 조직병리학적 변화에 미치는 영향을 조사하였다. 대조군은 생리식염수를 투여하였으며, 실험군은 해독정기탕 0.9 mL을 6시간, 24시간 간격으로 경구투여 하였다. 간기능의 지표가 되는 GPT 효소 활성은 해독정기탕 투여한 6시간 군에서 대조군에 비해 감소하였다. 항산화 효소인 SOD, catalase 활성도의 변화에 있어서도 6시간 실험군에서 변화를 보여주었고 24시간 경과 후에는 대조군과 실험군의 통계적인 유의성은 없었다. 간의 조직병리학적 관찰 결과 대조군은 심한 출혈, 간세포의 팽창과 중심정맥 내피세포의 파괴 현상이 뚜렷이 나타났으며, 24시간 경과 후에는 핵질의 응축과 사립체의 팽대현상이 현저하였다. 반면 해독정기탕 투여후 6시간 실험군은 일부 세포괴사와 세포사멸 보호 및 회복효과를 관찰하였다. 이상의 연구 결과로 보아 해독정기탕은 투여시간에 따라 간 기능회복 및 해독, 간세포의 항산화 활성변화, 세포사멸의 보호효과 약물로서 작용함이 사료된다.