• Safety and Health at Work
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• v.2 no.1
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• pp.57-64
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• 2011

Objectives: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. Conclusion: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.17-25
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• 2005

There are some critical drawbacks in the use of biomarkers for a global assessment of the toxicological impacts many chemicals and environmental pollutants have, primarily due to an individual biomarker's specificity for an explicit chemical or toxicant. In other words, the biomarker-based assessment methodology used to analyze toxicological effects lacks a high-throughput capability. Therefore, eco-toxicogenomics, or the study of toxicogenomics with organisms present within a given environmental locale, has recently been introduced with the advent of the so-called "-omics" era, which began with the creation of microarray technologies. Fish are comparable with humans in their toxicological responses and thus data from toxicogenomic studies performed with fish could be applied, with appropriate tools and implementation protocols, to the evaluation of environments where human or animal health is of concern. At present, there have been very active research streams for developing expression sequence tag (EST) databases (DBs) for zebra fish and rainbow trout. Even though few reports involve toxicogenomic studies with fish, a few groups have successfully fabricated and used cDNA microarrays or oligo DNA chips when studying the toxicological impacts of hypoxia or some toxicants with fish. Furthermore, it is strongly believed that this technology can also be implemented with non-model fish. With the standardization of DNA microarray technologies and ample progress in bioinformatics and proteomic technologies, data obtained from DNA microarray technologies offer not only multiple biomarker assays or an analysis of gene expression profiles, but also a means of elucidating gene networking, gene-gene relations, chemical-gene interactions, and chemical-chemical relationships. Accordingly, the ultimate target of eco-toxicogenomics should be to predict and map the pathways of stress propagation within an organism and to analyze stress networking.

• Environmental Analysis Health and Toxicology
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• v.20 no.1
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• pp.1-11
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• 2005

환경오염의 조기 경보 시스템으로 생체지표를 이용한 생태독성 모니터링이 최근 널리 연구되고 있다. 환경내의 생물종에서 측정한 생체지표를 이용한 환경 모니터링은 생태계 수준의 영향에 대한 예측 정보를 제공해 줄 수도 있다. 이를 위해서는 생체지표와 개체군 수준에서의 반응과의 인과관계가 밝혀져야 한다. 오염물질에 대한 생체의 반응은 분자, 세포, 생화학, 생리적, 개체, 개체군, 군집 수준에서 나타나게 되며, 이러한 각 단계별 반응은 반응 시간의 규모와 독성학적, 생태적 관련성에 따라 구분 지어 볼 수 있다. 각 개별 수준에서의 반응을 종합하면 오염물질에 노출된 생체의 전제적인 영향을 이해할 수 있으며, 이러한 이해를 바탕으로 개체군에서 나타나는 영향에 대한 인과관계를 추론할 수 있다. 생체지표와 개체군 수준의 반응과의 인과관계 정립은 효율적인 환경오염 예방기능 수행에 필수적인 과정이며, 다단계 생체 지표는 각 단계별 반응의 인과관계를 밝히기 위해 가장 적절한 접근 방법이다. 수서 무척추 생물인 Chironomus의 유충은 이러한 다단계 바이오마커 연구에 매우 적절한 생물학적 모델이다. 이 논문의 첫 번째 부분은 생체지표를 이용한 환경 모니터링을, 두 번째 부분은 Chironomus의 유충에서 생체지표의 적용에 대해서 다룬다.

• Environmental Analysis Health and Toxicology
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• v.21 no.4 s.55
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• pp.375-380
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• 2006

Endocrine disrupting chemicals (EDC) have been emphasized due to their threats in human health. Waste incinerator emission has been emphasized as a source of EDC including polychlorinateddibenzofurans(PCDD/F) and other carcinogenic polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene (1-OHP) has been used as an exposure biomarker for the PAHs. On the other hand, etheno-DNA adducts, e.g. 1, $N^6-ethenodeoxyadenosine({\varepsilon}dA)$, has been developed as an useful effective or response biomarker for carcinogenesis. Thus, I investigated association between urinary 1-OHP and ${\varepsilon}dA$ levels due to distance from an incinerator which was built more 10 years ago in the middle of a farm in P city. I designated the EDC-high and low exposed group due to distance from the incinerator, i.e. within 2.5km and $5.0{\sim}7.5km$ from the incinerator, respectively. The study subjects were age and sex-matched males and females (mean age, $61.3{\pm}9.6$ yrs; total 40 persons, male, 10; female, 10 for the each group). Urinary 1-OHP and ${\varepsilon}dA$ were analyzed with HPLC-FD and IP-HPLC-FD, respectively. As results, the distance from the incinerator was not associated with urinary 1-OHP nor ${\varepsilon}dA$ levels (p=0.43 and 0.82, respectively). On the other hand, urinary ${\varepsilon}dA$ levels were significantly higher in the hyperlipidemia group (N=10) than normal group (N=30). In conclusion, urinary 1-OHP nor ${\varepsilon}dA$ levels can not be suggested as an incinerator-related exposure nor effective biomarker. However, not only distance from the incinerator bot also systemic approaches including wind and soil contamination are required to assume exposure levels of incinerator-related EDC.

• Journal of Preventive Medicine and Public Health
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• v.45 no.4
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• pp.235-243
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• 2012

Objectives: Nail has been a substitute DNA source for genotyping. To investigate the integrity and consistency of nail DNA amplification for biomarker study, nail clippings from 12 subjects were collected at monthly intervals. The possibility of longer amplification and existence of GAPDH RNA/protein, were also investigated with three nail samples. Methods: Three primer sets were designed for quantitative amplification of nuclear and mitochondrial genes and analysis of their consistency. The mean threshold cycles in amplification of the target genes were compared to test the consistency of polymerase chain reaction (PCR) performance among individual factors including age groups, sex, family, the nail source, and by the size of the amplification segments. Results: The amplification of the target genes from nail DNA showed similar integrity and consistency between the nail sources, and among the serial collections. However, nail DNA from those in their forties showed earlier threshold cycles in amplification than those in their teens or seventies. Mitochondrial DNA (mtDNA) showed better DNA integrity and consistency in amplification of all three targets than did nuclear DNA (nucDNA). Over 9 kb of mtDNA was successfully amplified, and nested quantitative PCR showed reliable copy numbers (%) between the two loci. Reverse transcription PCR for mRNA and immunoblotting for GAPDH protein successfully reflected their corresponding amounts. Regarding the existence of RNA and protein in nails, more effective extraction and detection methods need to be set up to validate the feasibility in biomarker study. Conclusions: Nail DNA might be a feasible intra-individual monitoring biomarker. Considering integrity and consistency in target amplification, mtDNA would be a better target for biomarker research than nucDNA.

• Journal of Environmental Health Sciences
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• v.32 no.2 s.89
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• pp.164-170
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• 2006

Ethylene oxide is a genotoxic carcinogen with widespread uses as industrial chemical intermediate and gaseous sterilant. 2-hydroxyethylated N-terminal valine in Hb is a good biomarker for biological monitoring of ethylene oxide exposure, because of its stability. For measuring the hemoglobin adduct formed by exposure of ethylene oxide, we studied the determination of (N-2-hydroxy-ethyl)valine(HEV) in hemoglobin adduct by using GC/MS. Firstly we synthesized HEV with 2-amino-ethanol and bromoisovaleric acid(BIVA) and confirmed it with GC/MS-FID. Its fragmentations were m/z 116(base ion, M+-45) and m/z 130(M+-31). For measuring HEV with higher sensitivity, we use derivatives which were PFPITH(pentafluorophenylisothiocianate) and TBDMS (tributyldimethylsilylation) by using Edman procedure. Its fragmentation were m/z 425(M+-57), m/z 383(M+-99) and m/z 172(M+-310) by using GC/MS. We did biological monitoring for mice inhalation exposure with 400 ppm ethylene oxide. The concentrations of hemoglobin adduct were $168{\pm}3.8\;and\;512{\pm}04$(nmol g-1 globin) at 0.5 hr/day 400 ppm ethylene oxide inhalation exposure group, and $631{\pm}17\;and\;2265{\pm}9.4$(nmol g-1 globin) at 1.0 hr/day 400 ppm ethylene oxide inhalation exposure for 1 and 4 weeks, respectively. We confirmed that (N-2-hydroxy-ethyl)valine(HEV) of hemoglobin was a good biomarker for biomonitoring of ethylene oxide exposure, and can measured with derivatives such as PFPITH(pentafluorophenylisothiocianate) and TBDMS(tributyldimethylsilylation) by using GC/MS.

• Journal of Environmental Health Sciences
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• v.28 no.2
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• pp.173-182
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• 2002

Exposure to environmental tobacco smoke(ETS) increases the risk of lung cancer and other diverse health effect for nonsmokers. Health risk assessment of nonsmokers related to ETS exposure requires large and exact data of ETS exposure to nonsmokers. This study presented the data of ETS exposure to workers at three category of restaurants(Korean restaurant, coffee shop, wine shop) in Seoul. Markers of ETS exposure measured in this study were area and personal NO$_2$, area and urine nicotine, area respiratory suspended particulate(RSP) and urine cotinine. The mean concentration of RSP and nicotine of all restaurant indoor samples was 177.8$\mu\textrm{g}$/㎥(range:75.3~317.0$\mu\textrm{g}$/㎥) and 7.8$\mu\textrm{g}$/㎥(range:0~57.3$\mu\textrm{g}$/㎥). The mean concentration of urine cotinine measured for the biomarker of ETS exposure was 77.3ng/mL(range:17.3~174.6ng/mL). In all measurements, the concentration of ETS markers at the wine shop was higher than those at other restaurants. The correlation coefficient among the ETS markers measured in the study was significant between area RSP and nicotine concentration and between area NO$_2$and nicotine concentration.

• Journal of Environmental Health Sciences
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• v.30 no.4
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• pp.301-307
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• 2004

1,3-butadiene(DB) is a well-established rodent carcinogen, and a probable carcinogen to humans. This study was investigated the formation of hemoglobin adduct in ICR female mice inhaled with BD for 3 weeks (5 hr/day, 5 days/week). Body weights of mice were significantly low from onward day 4 or 9 of exposure comparing the control. Hemoglobin adducts formed by DB exposure were (N-2-hydroxy-3-butenyl) valine (HB Val adduct) and (N-2,3,4-trihydroxy-butyl)valine(THB Val adduct). The levels of HB Val adducts were 1.8, 3.7 and 6.2 pmol/mg globin for the 500 ppm BD inhalation group, and 5.7, 7.4 and 16.0 pmol/mg globin for the 1000 ppm BD inhalation group, when observed on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week after inhalation exposure, respectively. The levels of THBVal adducts were 32.0, 42.0 and 55.0 pmol/mg globin for the 500 ppm DB inhalation group, and 67.8, 72.7 and 83.5 pmol/mg globin for the 1000 ppm BD inhalation group, when observed on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week after inhalation exposure, respectively. Ratios of THBVal and HBVal adducts were higher at earlier exposure period and lower concentration. Ratios on the $1^{st},\;2^{nd},\;and\;3^{rd}$ week were 17.8, 11.4 and 8.87 for the 500 ppm BD inhalation group, and 11.9, 9.8 and 5.2 for the 1000 ppm BD inhalation group, respectively. In conclusion, THB Val and HB Val adducts were the important hemoglobin adducts in ICR female mice inhaled with BD, and the latter was more appropriate biomarker than the other for biological monitoring of BD exposure.

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.06a
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• pp.105-139
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• 2005

Increased signal in T1-weighted images was observed in the experimental manganese (Mn) poisoning of the non-human primate and a patient with Mn neurointoxication. However, our study showed that the increased signals in magnetic resonance images (MRI) were highly prevalent (41.6%) in Mn-exposed workers. Blood Mn concentration correlated with pallidal index. These changes in MRI tend to disappear following the withdrawal from the source of Mn accumulation, despite permanent neurological damage. Thus increased signal intensities on a T1-weighted image reflect exposure to Mn, but not necessarily manganism. Our study also showed that the concentration of Mn required to produce increased signal intensities on MRI is much lower than the threshold necessary to result in overt clinical signs of manganism. Increased signal intensities in the globus pallidus were determined by manganese accumulation in the animal experiment. Reanalysis of the previous data with the structural equation model revealed that pallidal index (Pl) on MRI reflects target organ dose of occupational Mn exposure

• Environmental Analysis Health and Toxicology
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• v.23 no.1
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• pp.47-51
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• 2008

The toxicity of environmental pollutants was measured between a image of the surface topography in HeLa cells using atomic force microscopy for the possibility of toxic effect measurement and environmental monitoring. A image of the surface topography by AFM were estimated as toxic endpoints. The surface topography by AFM was observed a change of the cell surface in the environmental pollutants, but the standard of the measurement requires for the dose-effect degree. The overall results indicate that the possibility of measurement using AFM were confirmed a dose-effect degree related toxic effects, but it requres correlation between more various biomarker and AFM's measurements if the possibility of the toxic effect measurement was established.