• Genomics & Informatics
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• 제7권4호
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• pp.187-194
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• 2009

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257, considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.

• Archives of Pharmacal Research
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• 제29권7호
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• pp.570-576
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• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• Plant Resources
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• 제2권1호
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• pp.26-30
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• 1999

Nitrate in edible vegetables is converted to nitrite by nitrate reductase(NR) and/or bacteria in intestines. Nitrite and amino, in the intestine of some animals and human, bind to form nitrosamine, which is toxic and known as carcinogen. This study was carried out to examine the effect of added chlorides and their concentrations on growth, yield and nitrate content in leaf lettuce plants in hydroponics. Seeds of lettuce cv, "Samsunjokchukmyon" were planted on April 29, and seedlings were planted on June 2, and were cultured until July 5 in 1998. KCI and CaCl₂ were used as chloride source and their concentrations were 1, 2 and 4 me/L, respectively, in the lettuce standard nutrient solution for National Horticultural Research Institute(NHRI). Completely randomized design with 3 replications was used. Nitrate content and NR activity were measured 2 and 5 weeks after planting(WAP). The obtained results were summarized as the follows : Leaf weight per plant was difference from harvest dates and treatments, but total leaf weight was not significantly different among treatments. Number of leaves was higher in KCI 2 me/L, CaCl₂1 me/L and control at 2 WAP than the others, and was higher in KCI 1 me/L, and control at 3 WAP than others, and was higher in control at 5 WAP. Total number of harvested leaves was the highest in control with 14, which followed by KCI 2 me/L and CaCl₂1 me/L. Nitrate content was decreased by addition of chloride in nutrient solution. Nitrate content in the 3rd and 9th leaves was significantly decreased. NR activity was higher in control and CaCl₂ addition treatments, while KCI addition treatments reduced NR activity. However, no direct relationship with nitrate was observed. Growth characteristics such leaf length and leaf width were not significantly influenced by chloride addition.

• Toxicological Research
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• 제35권2호
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• pp.137-154
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• 2019

Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.

• 대한의생명과학회지
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• 제26권4호
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• pp.288-295
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• 2020

Infection of Helicobacter pylori on gastric mucosa is associated with various gastric diseases. According to the WHO, H. pylori causes gastric cancer and has been classified as a class I carcinogen. Riboflavin is an essential vitamin which presents in a wide variety of foods. Previous studies have shown that riboflavin/UVA was effective against the growth inhibition of Staphylococcus aureus, S. epidermidis and multidrug-resistant Pseudomonas aeruginosa and had the potential for antimicrobial properties. Thus, we hypothesized that riboflavin has a potential role in the growth inhibition of H. pylori. To demonstrate inhibitory concentration of riboflavin against H. pylori, we performed agar and broth dilution methods. As a result, we found that riboflavin inhibited the growth of H. pylori. The MIC was 1 mM in agar and broth dilution test. Furthermore, to explain the inhibitory mechanism, we investigated whether riboflavin has an influence on the replication-associated molecules of the bacteria using RT-PCR to detect mRNA expression level in H. pylori. Riboflavin treatment of H. pylori led to down-regulation of polA and dnaB mRNA expression levels in a dose dependent manner. After then, we also confirmed whether riboflavin has cytotoxicity to human cells. We used AGS, a gastric cancer cell line, and treated with riboflavin did not show statistically significant decrease of cell viability. Thus, these results indicate that riboflavin can suppress the replication machinery of H. pylori. Taken together, these findings demonstrate that riboflavin inhibits growth of H. pylori by inhibiting replication of the bacteria.

• 한국환경보건학회지
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• 제47권4호
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• pp.356-365
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• 2021

Background: Concerns have been raised regarding the criteria of groundwater, in particular in Gwangwon-do Province where many residents drink groundwater due to the poor supply of tap water and a high nonconformity rate with water quality criteria nationwide. Objectives: Water quality monitoring and risk assessment were conducted for groundwater in Hoengseong, Gangwon-do Province. Methods: A total of 46 items required for meeting drinking water criteria were analyzed from 258 samples collected from March 2017 through August 2018 (152 sites in 2017 and 106 sites in 2018). Risk assessment was conducted for two non-carcinogens (F^- and NO₃-N), and one carcinogen (i.e., arsenic) based on their high nonconformity to water quality criteria. Results: Water quality analysis revealed that the total proportion of nonconformities was determined to be 27.9%. The nonconformity rate for each content item is as follows: total colony counts (1.6%), total coliform (6.2%), Escherichia coli (1.2%), F^- (8.1%), arsenic (4.7%), NO₃-N (8.1%), pH (1.2%), manganese (0.4%), and turbidity (5.8%). Risk assessment indicated that fluoride induced a hazard quotient greater than 1 with the 95% UCL (Upper Confidence Limit) concentration of the total 258 sites and average, median, and 95% UCL concentrations of nonconformity sites. For NO₃-N, there was no human health risk. For arsenic, the excess cancer risk exceeded the acceptable cancer risk of 1×10^-6 with the average and 95% UCL concentrations of total 258 sites and average, median, and 95% UCL concentrations of nonconformity sites. Conclusions: This study suggests that it is necessary to expand water quality monitoring of groundwater and conduct a more detailed risk assessment in order to establish a health care plan for the residents of Hoengseong, Gangwon-do Province.

• 인간식물환경학회지
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• 제23권5호
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• pp.537-544
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• 2020

Background and objective: Artemisia argyi has a long history as an effective treatment for various diseases. The detection of environmental pollutant benzo(a)pyrene, a known human carcinogen, in the leaves of Artemisia argyi is cause for concern. For medicinal plant extracts, both a reduction of benzo(a)pyrene as well as the maintained effectiveness of the compound are important. Therefore, in this study, we propose an optimized process for the addition and filtration of activated carbon to reduce benzo(a)pyrene and change the contents of the indicating substance(jaceosidine and eupatilin). Methods: Artemisia argyi EtOH extract containing 36 ppb of benzo(a)pyrene was added to 0.1, 0.5, 1.0, and 1.5% (w/w) of activated carbon for 120 min and filtered using an activated carbon filter 1, 2, 3, and 5 times respectively. The content of benzo(a)pyrene and indicating substances in Artemisia argyi extract were then measured with high performance liquid chromatography (fluorescence and UV detectors). Results: As the amounts of activated carbon powder and filtering cycles increased, the content of benzo(a)pyrene in the Artemisia argyi extract decreased. However, when activated carbon powder 1.5% was added to the extract, and when the activated carbon filter was filtered five times, the results were reduced by 15% and 30~40% respectively. The optimal extraction condition for reducing benzo(a)pyrene was adding 1.5% of activated carbon powder. This resulted in reducing benzo(a)pyrene by 83% and indicating substances by about 4%. Conclusions: Here we present a process for reducing benzo(a)pyrene in Artemisia argyi extract using activated carbon to reduce toxicity and minimize the loss of active ingredients. This approach has potential application within a manufacturing process of various medicinal plant extracts.

• Tuberculosis and Respiratory Diseases
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• 제47권4호
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• pp.471-477
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• 1999

연구배경 : 발암물질의 체내 대사효소계인 GSTM1, T1과 NAT1의 유전적다형성의 발현 양상이 폐암발생과 연관성이 있는가를 밝히기 위해 환자-대조군 연구를 수행하였다. 방 법 : 서울대병원에서 병리화적 폐암환자군으로, 비암성요료계질환으로 입원한 환자를 대조군으로 설정하여, 각 환자에 대한 성, 연령, 흡연력 등을 병력조사나 병록지검토로 얻었으며, 말초혈액을 채취하여 DNA를 분리한 뒤, 다중중합효소연쇄반응을 이용하여 GSTM1, T1의 유전자형을, nested PCR법을 이용하여 NAT1의 유전자형을 결정하였다. 결 과 : 모집된 환자, 대조군은 각각 118 명, 150명이었고, 환자군에서 흡연력은 통계적으로 의미있게 높았다(p<0.05). GSTM1의 소실형은 비소실형에 비해 편평상피암의 위험을 높였으나(OR=2.25 ; 95% CI=1.12-4.51), GSTT1의 경우는 폐암의 위험인자로 작용하지 않았다. NAT1의 fast acetylator형은 폐암환자전체를 분석했을 때 통계적으로 의미있는 위험도 상승을 보였다(OR=2.13; 95% CI=1.04-4.40). 결 론 : GSTM1의 소실형과 NAT1의 fast형은 폐암발생과 관련성이 있다.

• 한국산업보건학회지
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• 제24권4호
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• pp.446-452
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• 2014

Objective: This study aimed to evaluate the exposure status of formaldehyde(FA) among the nurses in ambulatory care departments of university hospital. Methods: Two university hospitals were surveyed. The FA concentration in air were measured to target 62 nurses in 8 ambulatory care departments(89 samples). Air sampling and analysis of FA were carried out according to the OSHA Method ID-205. The survey was conducted with questionnaire asking about how to control FA and whether the nurses use the formaldehyde protectors or not. Results: FA was detected in all samples. The maximum concentration of FA was 0.258 ppm and the geometric mean was 0.023 ppm. There was no sample that exceeded any of exposure standards by OSHA-TWA whereas there were 54 samples(60.7%) that exceeded the standards by NOISH-TWA. Among 62 nurses handling FA, 13 nurses(21.0%) used the protective gloves while nobody used a gas mask. It was assessed that any of 8 common ambulatory care departments did not use a safety cabinet for FA in which local exhaust ventilation was fixed. Conclusions: Nurses in ambulatory care departments were exposed to FA. Therefore, the environment management of a workplace, the health management of a nurses, FA handling education and installing a FA cabinet with a local exhaust ventilation were needed because FA as a carcinogen was able to cause any cancer to a human body if it was emitted in air for long time.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권4호
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• pp.373-382
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• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.