• 대한임상독성학회지
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• 제10권1호
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• pp.22-32
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• 2012

Purpose: The purpose of this study was to examine the occurrence of toxic exposure cases in Korean emergency centers using a toxic exposure surveillance system-based report form and to provide guidelines for the prevention and treatment of toxic exposures. Methods: We retrospectively reviewed the medical records of toxic exposure patients who had visited emergency centers from January 2009 to December 2009. Epidemiology data points for the toxic exposure cases included age, gender, type of exposure, number and kind of substances involved, reason and route of poison exposure, management of the patients in the emergency departments, and the clinical outcome. Results: A total of 3,501 patients from 12 emergency departments were enrolled in the study. 50.0% of the total exposure patients were male and 63.0% of the total cases were fatal. Acute intoxication occurred in 91.3% of the total patients and suicidal intent was the most common (43.3%) reason for exposure. The most common route of exposure was ingestion (75.9%). Of the total cases, pesticides were involved in 26.3%, sedatives/hypnotics/antipsychotics were involved in 22.0%, and bites and envenomations were involved in 15.7%. Conclusion: We provided a database of patients who were admitted to emergency departments after poisoning incidents. We recommend that toxicology professionals develop a classification scheme for toxicants which is adequate for Korean domestic circumstances and initiate a toxic surveillance system for all types of exposures. With support of a psychiatric surveillance system for suicidal patients and establishment of social mediation for pesticide poisoning, major reductions in poison exposures can be achieved.

• International Journal of Oral Biology
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• 제37권2호
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• pp.43-50
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• 2012

The use of high throughput screening (HTS) in drug development is principally for the selection new drug candidates or screening of chemical toxicants. This system minimizes the experimental environment and allows for the screening of candidates at the same time. Umbilical cord-derived stem cells have some of the characteristics of fetal stem cell and have several advantages such as the ease with which they can be obtained and lack of ethical issues. To establish a HTS system, optimized conditions that mimic typical cell culture conditions in a minimal space such as 96 well plates are needed for stem cell growth. We have thus established a novel HTS system using human umbilical cord derived-mesenchymal stem cells (hUC-MSCs). To determine the optimal cell number, hUC-MSCs were serially diluted and seeded at 750, 500, 200 and 100 cells per well on 96 well plates. The maintenance efficiencies of these dilutions were compared for 3, 7, 9, and 14 days. The fetal bovine serum (FBS) concentration (20, 10, 5 and 1%) and the cell numbers (750, 500 and 200 cells/well) were compared for 3, 5 and 7 days. In addition, we evaluated the optimal conditions for cell cycle block. These four independent optimization experiments were conducted using an MTT assay. In the results, the optimal conditions for a HTS system using hUC-MSCs were determined to be 300 cell/well cultured for 8 days with 1 or 5% FBS. In addition, we demonstrated that the optimal conditions for a cell cycle block in this culture system are 48 hours in the absence of FBS. In addition, we selected four types of novel small molecule candidates using our HTS system which demonstrates the feasibility if using hUC-MSCs for this type of screen. Moreover, the four candidate compounds can be tested for stem cell research application.

• Applied Microscopy
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• 제34권4호
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• pp.241-254
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• 2004

신장은 독성물질, 빈혈, 재관류-유도 상해, 급성신부전에 회복 기능을 가지고 있다. 뇨 표피성장인자(EGF)는 신장 사구체연접장치에서 생산된다. 신장은 EGF를 축적하거나 배설한다. 신장 질환의 경우에는 EGF 배설이 감소한다. 본 연구에서는 glycerol-유도 급성신부전에서 스쿠알렌의 효과를 연구하였다. In vitro에서 RT-PCR를 통해 EGF 발현을 관찰하였다. 근위세뇨관 세포를 분리한 후, glycerol (1, 2, 4 mM) 혹은 스쿠알렌(0.1, 0.05 or 0.1%)을 첨가하였다. In vivo에서 BUN, creatine, 조직학적 변화를 관찰하였다. 실험군은 다음과 같다. 실험군 1은 정상군, 실험군 2는 glycerol (50%, 8 ml/kg) 처치 후, 스쿠알렌을 처치하지 않은 군, 실험군 3은 glycerol (50%, 8 ml/kg) 처치 후, 스쿠알렌(180 mg/kg)을 함께 처치한 군으로 각 실험군 당 생쥐 7마리를 사용하였다. 실험 결과, glycerol이 신장에 손상을 주어 EGF mRNA 발현이 감소됨을 확인할 수 있었다. 그러나, 스쿠알렌을 처치한 군에서는 EGF mRNA 발현이 증가함을 관찰할 수 있었다. 또한, BUN과 creatine 수치의 빠른 회복이 관찰되었다(P<0.01). 조직학적 관찰에서도 실험군 2는 사립체의 심한 손상이 관찰되었는데, 실험군 3의 경우 사립체의 빠른 회복이 관찰되었다. 결론적으로, 스쿠알렌이 glycerol-유도 급성신부전에 회복 효과가 있을 것으로 사료된다.

• Toxicological Research
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• 제20권1호
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• pp.71-82
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• 2004

Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.

• 생명과학회지
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• 제19권6호
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• pp.799-803
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• 2009

방사선 및 각종 독성물질에 의한 고환 정세관세포의 사멸은 apoptosis와 관련이 있다고 알려져 있으나 정세관상피주기에 따른 apoptosis 발생에 대한 변화연구는 미진하다. 본 연구에서는 감마선을 조사한 ICR 마우스의 고환에서 apoptosis 발생을 transferase-mediated end labeling (TUNEL) 과 periodicacid-Schiff (PAS) 염색을 동시에 실시하여 관찰하였다. Apptosis는 TUNEL 양성으로 나타났으며 특징적 형태변화를 보였다. 2 Gy (분당 2 Gy의 선량률)의 방사선을 조사하고 24시간동안의 변화를 관찰한바 방사선조사 후 12시간에 가장 높은 apoptosis 발생을 보였고 이후 감소하였다. 8 Gy까지의 방사선을 조사하고 8시간에 변화를 관찰한 결과 모든 정세관상피주기에서 방사선 용량에 비례한 apoptosis의 발생이 관찰되었다. 방사선 용량-반응은 linear-quadratic 곡선 [y=(-0.014${\pm}$0.009)$D^{2}$ +(0.31${\pm}$0.697)D+0.3575. Y는 정세관 당 TUNEL 양성세포의 수, D는 방사선 용량(Gy), $r^{2}$=0.9]에 가장 일치 하였다. 최대반응은 8 Gy에서 관찰되었으며, 0.5 Gy조사군에서도 변화가 나타났다. 이러한 변화는 정세관상피주기 V에서 B정조세포와 정세관상피주기 XII의 분열기 정자세포에서 가장 현저하였다.

• Applied Biological Chemistry
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• 제31권3호
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• pp.226-233
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• 1988

수도작(水稻作)에 있어 주요한 병해(病害)의 하나인 문고병(紋枯病)을 조기(早期)에 생력적(省力的)으로 방제할 수 있는 신농약제형(新農藥劑型)의 개발가능성을 검토(檢討)하기 위하여 pencycuron과 flutolanil을 유효성분으로 하고 식물성유지(植物性油脂)와 계면활성제(界面活性劑)를 각각 부유제(浮遊劑) 및 확전제(擴展劑)로 사용하여 4%의 수면부유제(水面浮遊劑) 시제품(試製品)을 제조(製造), 그의 이화학성(理化學性)과 생물효과를 조사(調査)한 바 다음과 같은 결과를 얻었다. 시제품(試製品)의 수면확전성(水面擴展性)은 $35cm^2/mg$ 이상으로 우수하였으며 담수중(湛水中) 유효성분의 분포(分布)는 pencycuron 시제품(試製品)이 수표면(水表面)에 존재한 반면 flutolanil은 담수중(湛水中)으로의 확산(擴散)이 용이하였다. 시제품(試製品)은 사용(使用)한 부제(副劑)의 종류(種類)에 관계없이 모두 주성분(主成分)의 경시분해(經時分解)가 완만하여 화학적(化學的)으로 안정(安定)하였다. 실험실하(實驗室下)에서 pencycuron 시제품(試製品)의 균핵발아저지력(菌核發芽沮止力)은 30일 이상 지속하였다. 친유성(親油性) 계면활성제(界面活性劑)를 사용하여 제조한 pencycuron 시제품(試製品)은 수도유묘이앙(水稻幼苗移秧) 1일(日) 전(前)에 유효성분으로 20g/10a을 수면살포(水面撒布)하였을 매 수화제(水和劑)와 동등한 방제효과가 있었다. 약제처리후(藥劑處理後) 5일 이내의 담수범람(湛水汎濫)은 방제효과를 현저히 저하시켰다.

• 한국산업보건학회지
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• 제25권2호
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• pp.134-145
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• 2015

Objectives: An objective of this study was to perform a risk assessment and social cost-benefit analysis for revising permissible exposure limits for seven substances: Nickel(Insoluble inorganic compounds), benzene, carbon disulfide, formaldehyde, cadmium(as compounds), trichloroethylene, touluene-2,4-diisocyanate. Materials and Methods: The research methods were divided into risk and hazard assessment and cost-benefit analysis. The risk and hazard assessment for the seven substances consists of four steps: An overview of GHS MSDS(1st), review of document of ACGIH's TLVs (2nd), comparison between international occupational exposure limits and domestic permissible exposure limits(3rd), and analysis of excess workplace and excess rate for occupational exposure limits based on previous work environment measurement data(4th). Total cost was estimated using cost of local exhaust ventilation, number of excess workplace and penalties for exceeding a permissible exposure limit. On the other hand, total benefit was calculated using the reduction rate of occupational disease, number of workplaces treating each substance and industrial accident compensation. Finally, the net benefit was calculated by subtracting total cost from total benefit. Results: All the substances investigated in this study were classified by CMR(Carcinogens, Mutagens or Reproductive toxicants) and their international occupational exposure limits were stricter than the domestic permissible exposure limits. As a result of excess rate analysis, trichloroethylene was the highest at 11%, whereas nickel was the lowest at 0.5%. The excess rates of all substances except for trichloroethylene were observed at less than 10%. Among the seven substances, the total cost was highest for trichloroethylene and lowest for carbon disulfide. The benefits for the seven substances were higher than costs estimated based on strengthening current permissible exposure limits. Thus, revising the permissible exposure limits of the seven substances was determined to be acceptable from a social perspective. Conclusions: The final revised permissible exposure limits suggested for the seven substances are as follows: $0.2mg/m^3$ for nickel, 0.5 ppm(TWA) and 2.5 ppm(STEL) for benzene, 1 ppm(TWA) for carbon disulfide, $0.01mg/m^3$(TWA) for cadmium, 10 ppm(TWA) and 25 ppm(STEL) for trichloroethylene, 0.3 ppm(TWA) for formaldehyde, and 0.005 ppm(TWA) and 0.02 ppm(STEL) for toluene diisocynate(isomers).

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.256-261
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• 2005

The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

• 한국환경농학회지
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• 제2권2호
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• pp.108-113
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• 1983

환경독성학(環境毒性學)(ecotoxicology) 관점(觀點)에서의 연구분야(硏究分野)는 크게 bioassay의 평가기법(評價技法)과 ecosystem analysis를 위한 야외조사(野外調査)로 대별(大別)된다. 본 연구(硏究)는 현재 다량(多量) 사용(使用)되고 있는 제초제(除草劑)(butachlor), 살충제(殺蟲劑)(carbofuran), 살균제(殺菌劑)(tricyclazole)를 철포(撤布)한 논에서의 periphyton에 대한 농약(農藥)의 영향(影響)을 평가(評價)하였다. 1) Periphyton 중(中) 기초생산자(基礎生産者)인 algae의 chlorophyll-a 함량(含量)은 벼 생육기간(生育期間)동안 $0.0007{\sim}0.0091g/^2$를 나타내었으며 전반적으로 농약(農藥)에 의한 chlorophyll-a 함량(含量)의 영향(影響)은 없었으며 수온(水溫)과 일조량(日照量)에 따른 변화(變化)를 나타내었다. 2) 생체량(生體量)(dry and ash-free weight)은 $0.0535{\sim}2.9850g/^2$로 biomass 역시 수온변화(水溫變化)에 따른 영향(影響)으로 사료(思料)된다. 3) Autotrophic index는 $43{\sim}2027$의 값을 나타내었다. 논에서 형성(形成)되는 periphytic community는 대부분 heterotrophic 조건(條件)을 갖는 것으로 평가(評價)된다. 이것은 biomass 구성체(構成體)가 기초생산자(基礎生産者)보다는 유기물질(有機物質)과 소비자(消費者)가 많은 trophic nature를 의미하는 것이다. 이상의 결과(結果)로 미루어 볼 때 논에서 사용(使用)하고 있는 제초제(除草劑)를 비롯한 살충제(殺蟲劑), 살균제(殺菌劑)등의 농약(農藥)은 논토양의 부착성 조류(藻類)의 생육(生育) 및 biomass에 큰 영향(影響)을 미치지 않는 것으로 사료(思料)된다. 그러나 본(本) 실험(實驗)은 한정(限定)된 지역에서 1년간(年間)이라는 단기간의 조사 기간동안 실시된 것이고, 또한 실험실적(實驗室的)으로 bioassay 기법에 의한 algae의 영향(影響)을 평가(評價)하지 않았기 때문에 위의 결과(結果)만으로 어떤 사실을 단정하기 곤란하므로 이 연구(硏究)를 바탕으로 하여 생태계내(生態系內) 1차 생산자인 조류(藻類)에 대한 농약(農藥)의 영향(影響)을 광범위하며, 깊이 있는 연구(硏究)와 자료축적(資料蓄積)으로 환경독성학(環境毒性學) 분야(分野)를 발전(發展)시켜야 할 것이다.

• 대한수의학회지
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• 제44권3호
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• pp.379-387
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• 2004

When an organism is exposed to various toxicants chronically, reactive oxygen species(ROS) are accumulated and eventually result in several biological effects from gene expression to cell death. In the present study we investigated the oxidative damage of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD) and/or benzo(a)pyrene (B(a)P) in C100 cells. C100 cells treated with TCDD(30 nM) and B(a)P($3{\mu}M$) underwent diverse oxidative stress as determined through thiobarbituric acid-reactive substances(TBARS) formation, DNA fragmentation, DNA single strand break(SSB) assay, immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine(8-OHdG), and mRNA expressions of antioxidant enzymatic genes such as Cu/Zn-SOD gene, GPx(glutathione peroxidase 5) gene, and catalase gene. Lipid peroxidation in C100 cells was determined through measuing the formation of TBARS. For theat, the cells were pretreated with TCDD(30 nM) and/or B(a)P($3{\mu}M$) for 0.5, 1, 2 and 4 days. TBARS formation was increased in TCDD(30 nM) and B(a)P($3{\mu}M$) and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) and positive control treatment groups comparing to the controls. Mixture treatment induced more DNA fragmentation than the single treatment group at day 6. Also, SSB in all treatment groups was clearly observed when compared with the negative control group. As with the expression of antioxidant enzyme, GPx 5mRNA, B(a)P alone and mixture($30nM\;TCDD+3{\mu}M\;B(a)P$) treatment were higher comparing to those of the negative control and TCDD treatment groups. Our results suggest that exposure of C100 cells to mixture of TCDD and B(a)P leads to significant oxidative damage comparing to the exposures to the individual chemicals. Mechanisms of action are discussed. Additional studies are needed to elucidate the detailed mechanism of mixture-induced toxicity.