• Environmental Engineering Research
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• 제11권5호
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• pp.277-284
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• 2006

The genetic toxicity of environmental pollutants, namely, nonylphenol (NP), bisphenol A (BPA) and chloropyriphos (CP) was investigated in aquatic sentinel species, freshwater crustacean, Daphnia magna, and larva of aquatic midge, Chironomus tentans, using Comet assay. Physiological effect of such pollutants was also investigated by studying the specimens' rates of reproduction, growth and survival. Acute toxicity results showed that, as expected, Daphnia was more sensitive than Chironomus to chemical exposure. The order of acute toxicity was CP > NP > BPA in D. magna and NP > CP > BPA in C. tentans. BPA may exert a genotoxic effect on D. magna and C. tentans, given that DNA strand breaks increased in both species exposed to this compound, whereas NP- and CP-induced DNA damage occurred only in C. tentans. In vivo genotoxic data obtained in aquatic sentinel species could provide valuable information for freshwater quality monitoring. The experiments with NP-exposed D. magna showed that the pollutant has long-term effects on reproduction, whereas no short-term effect on DNA integrity was found, being an example of a false-negative result from the biomarkers perspective. This result could be interpreted that other mechanism than genetic alteration might be involved in NP-induced reproduction failure in D. magna. False-positive results from the genotoxic biomarker obtained in BPA-exposed D. magna and in NP-exposed C. tentans make it difficult to use DNA integrity as an early warning biomarker. However, as the mere presence of genotoxic compounds, which are potentially carcinogenic, is of high concern to human and ecosystem health, it could also be important to rapidly and effectively detect genotoxic compounds in the aquatic system in ways that do not necessarily accompany a higher level of alteration. Considering the potential of D. magna and C. tentans as bioindicator species, and the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information for environmental risk assessment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9955-9960
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• 2014

Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. Materials and Methods: A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controls were included in this study. Methylation specific PCR was used to determine the MGMT methylation status in serum samples. Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophageal cancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betel quid and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smoking habit synergistically with MGMT methylation elevated the risk for esophageal cancer development [adjusted OR=5.02, 95% CI=1.35-18.74; p=0.010 for tobacco chewing and Adjusted OR=3.00, 95% CI=1.22-7.36; p=0.014 for tobacco smoking]. Conclusions: Results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by the environmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer in high incidence region of North East India.

• 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.

• Journal of Radiation Protection and Research
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• 제18권2호
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• pp.61-69
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• 1993

우라늄 피폭후 효소활성도가 내부피폭의 biomarker로서의 가능성을 연구하기 위하여 수서생물인 잉어(Caprinus carpio)의 복강내 우라늄 투여시 간조직에서 일어나는 여러가지 효소계의 변화를 조사하였다. 이러한 효소활성도의 변화는 우라늄 내부피폭의 biomarker로서 가능성을 가지고 있으며 연구결과는 다음과 같다. 1) 6일째까지 우라늄을 주사하여 적출한 간에서의 전체단백질량은 계속 감소하고 있다. 2) 세포내의 lysosome내에 함유하고 있는 acid pretense와 ${\beta}-glucuronidase$의 활성도는 6일째 투여후까지 활성도가 감소하고 있다. 3) Alkaline phosphatase의 경우 6일째 우라늄 투석후까지 증가하고 있으며 반대로 acid phosphatase의 경우 6일째 우라늄 투여후까지 활성도가 급격히 증가하였고 glutamate oxaloacetate transaminase의 활성도는 완만하게 증가하고 있다. 4) Creatine kinase의 활성도는 완만한 감소를 보이고 있으며 malate dehydrogenase는 첫번 우라늄 투여후에 활성도가 급격히 감소하였고 3일째 우라늄 투여후에는 활성도가 거의 나타나지 않았다.

• 한국군사과학기술학회지
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• 제21권2호
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• pp.246-254
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• 2018

Psychological stress and physical fatigue, such as anxiety, fear, sleep disturbance, etc., caused by exposure to the war, can lead to post-traumatic stress syndrome(PTSD) or war syndrome. The military has also prepared for drug use to minimize war syndrome and preserve combat strength. However, efforts to prevent war syndrome are still lacking. This study was conducted to identify biomarkers that can track psychophysiological changes. Psychophysiological changes associated with PTSD can be divided into four main categories. The four categories are behavioral changes, changes in brain cognition, neuroimmunological changes, and changes in innate immunity. This study suggest that biomarker profile can be made by the distance moved and the anxiety-like behavior in the open field for behavior category, brain BDNF levels in the brain cognition category, serum corticosterone in the neuroimmunology category, and inflammatory cytokine levels in the innate immunity category.

• 생태와환경
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• 제48권2호
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• pp.86-94
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• 2015

Chironomous is aquatic insect belonging to order Diptera, family Chironomidae. Their larval stage can be found mainly in aquatic benthic environment, hence good model organism to study environmental toxicology assessments and consider as useful bio indicators of contamination of the aquatic environment. In this study, Chironomus Heat Shock Proteins, Cytochrome 450, Glutathione S-transferase, Serine-type endopeptidase gene expressions were compared between polluted field areas (Chironomus plumosus) and under laboratory conditions (Chironomus riparious) to investigate molecular indicators for environmental contaminant stress assessment. Heavy metal (Al, Fe, Mn, Cu, Cr, Zn, Se, Pb, As, Cd) concentrations in sediments collected from three study areas exceeded the reference values. Moreover, HSPs, CYP450 and GST gene expression except SP for C. plumosus showed higher expression than C. riparious gene expression. Similar gene expression pattern was observed in C. riparious that exposed environment waters up to 96 h when compared to C. plumosus exposed to waters that grown in lab conditions. In summary, this comparative gene expression analysis in Chironomous between field and laboratory condition gave useful information to select candidate molecular indicators in heavy metal contaminations in the environment.

• 한국해양생명과학회지
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• 제2권1호
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• pp.34-38
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• 2017

FK506BP는 일명 FK506 binding protein 12이라 불리는 작은 펩티드로서 single 도메인을 가진다. FK506BP는 면역반응 억제, 산화적 스트레스 및 염증과 관련이 있다. 본 연구의 목적은 참돔(Pagrus major)을 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에 노출시킨 후, FK506BP 유전자의 발현을 관찰하는 것이다. 연구결과, FK506BP 유전자의 발현은 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu)상태에서 유의적으로 증가하는 것으로 나타났다. 이 연구결과로서 FK506BP 유전자는 수온 및 염분 등의 환경 스트레스에 대한 생체지표유전자로서 역할을 한다고 제의한다.

• 한국해양생명과학회지
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• 제2권2호
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• pp.70-74
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• 2017

IL-1RAcP는 일명 interleukin-1 receptor accessory protein이라 칭하며 interleukin-1 염증성 사이토카인과 interleukin-1 receptor I (IL-1RI) 결합체와 복합체를 형성하여 작용한다. IL-1RAcP는 면역반응, 스트레스 및 세포사멸과 관련이 있다. 본 연구의 목적은 참돔(Pagrus major)을 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에 노출시킨 후, IL-1RAcP 유전자의 발현을 관찰하는 것이다. 연구결과, IL-1RAcP 유전자의 발현은 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에서 유의적으로 증가하는 것으로 나타났다. 이 연구결과로서 IL-1RAcP 유전자는 저수온 및 저염분 등의 환경 스트레스에 대한 생체지표유전자로서 역할을 한다고 제의한다.

• 한국산업보건학회지
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• 제17권1호
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• pp.43-52
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• 2007

This study was designed to investigate the difference of airborne lead concentration by type of lead industries and type of lead exposure and to evaluate their association with lead biomarkers of lead workers in 11 lead using industries. Total of 182 lead workers (male: 167, female: 15) from 11 lead industries were participated for this study from March, 2004 to August, 2005. Airborne lead concentration were measured by representative personal sampling of workers in each unit workplace and applied same concentration value to the workers in the same unit workplace who did not measure their airborne lead with personal air sampling. Tibia lead, blood lead, zinc protoporphyrin in whole blood, ${\delta}$-aminolevulinic acid in urine, hemoglobin and hematocrit were selected as study variables of indices of lead exposure. Information about type of lead exposure (fume or non-fume other), age, work duration, smoking & drinking habit were also collected. Significant differences were seen in the means of zinc protoporphyrin, blood lead and tibia lead in lead workers by different airborne lead concentration in workplace. While blood lead and tibia lead in lead workers were significantly higher in secondary smelting than other types of lead industries, zinc protoporphyrin, ${\delta}$-aminolevulinic acid in urine and airborne lead concentration were significantly higher in litharge manufacturing. While the mean blood lead was significantly higher in the lead workers working in fume type unit workplace than those of non-fume lead workers, the mean airborne lead concentration of fume workers was significantly lower than non-fume lead workers. In the multiple regression analysis of airborne lead concentration and the type of lead exposure on tibia lead and lead exposure indices after adjustment of related covariates, airborne lead concentration was statistically significantly associated with blood lead and tibia lead, but the type of lead exposure was only associated with blood lead. To verify the causal association of airborne lead concentration on blood lead and tibia lead, further studies are needed.

• Nutrition Research and Practice
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• 제4권5호
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• pp.351-355
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• 2010

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.