• 대한약침학회지
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• 제19권1호
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• 한국대기환경학회지
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• 제34권2호
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• pp.233-243
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• 2018

This study was carried out to characterize the ambient levels of PAH concentrations in Pohang city, where steel industry has been intensively developed. A large amount of PAH emissions from steel production and related industries in Pohang are concerned about the environmental health hazards of nearby residents. TSP samples were seasonally collected during 10 days at four sites in Pohang from April to December 2010. Each sample was collected for 24 hours using high-volume air sampler. All samples were extracted by $soxtec^{TM}$ before concentration of 1.0 mL. The concentrates were analyzed by GC/MS. The prevailing wind direction was southwest and west-southwest in Pohang during the measurement period. Variations of TSP concentrations appeared to be similar between four sites. The highest TSP concentration was found in fall, while the lowest in summer. The highest PAH concentration was found at an industrial site, while the lowest at a residential/commercial site. In the case of BaP, the average concentration at the industrial site was $0.63{\pm}0.66ng/m^3$, which was approximately 2 times of the residential/commercial site. The paired t-test (p<0.05) showed significant differences between industrial and residential area. Particulate PAH concentrations were higher in the winter and lower in the summer. The concentrations of BaP in winter were 2~10 times higher than those in the other three seasons. This study clearly demonstrated the impact of steel industry on the elevated levels of PAH in Pohang city.

• 한국양식학회지
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• 제18권3호
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• pp.200-206
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• 2005

We previously pointed out that the polluted sediment elutriate manifestly affected the early events of reproductive outputs in the Pacific oysters, Crassostrea gigas. A serial dilution of priority xenobiotic sediment elutriates determined by gas chromatography/mass spectrometry (GC/MS) were exposed to gametes of the oyster with different stress burdens to detail the maternal stress transfer to its reproductive outputs. There was an apparent critical concentration over which survival and morphogenesis were significantly affected with more profound damage in morphogenesis. The critical concentration which drives mortality and abnormal morphogenesis of the larvae corresponded to a dilution between 10 and 20% of our elutriate. The adverse effects of the early lives by the xenobiotic exposure over the critical concentration were magnified by the maternal stress from the exposed benzo(a)pyrene (BaP), one of the priority polyaromatic hydrocarbons (PAHs) during the maturation condition. These results indicate that maternal transfer of the xenobiotic compounds from oysters living in the contaminated location might represent a significant adverse effect to their larval population of wild seeds.

• 한국입자에어로졸학회지
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• 제20권1호
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• pp.13-24
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• 2024

The concentrations of polycyclic aromatic hydrocarbons (PAHs) and elemental carbon (EC) in particulate matter, typical primary aerosols have decreased in Seoul between 2003 and 2018 (80% for PAHs and 85% for EC). The yearly mean benzo[a]pyrene (BaP) concentration has been lower than 1 ng/m3 since 2010-2011, the target value set by the European Union (EU) and China. A series of policies related to solid fuel and vehicle in South Korea and China should be effective in the reduction of the ambient PAHs and EC concentrations. But the emission data of PAHs and EC at both countries did not support that hypothesis. Possible causes are uncertainties in the emission inventories of primary carbonaceous aerosols in South Korea and China, although there may be a minor effect of the emissions from North Korea on the concentrations in Seoul. Thus the further policy directions against PAHs and EC such as improvements of emissions inventories and measurements, intensive regulation of non-road mobile sources and control of PAHs derivatives are discussed.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.474-478
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• 1999

Modulation of unscheduled DNA synthesis by dehydroepiandrosterone (DHEA) after exposure to various chemical carcinogens was investigated in the primary rat hepatocytes. Unscheduled DNA synthesis was induced by treatment of such direct acting carcinogens as methly methanesulfonate (MMS) and ethyl methanesulfonate (EMS) or procarcinogens including benzo(a)pyrene (BaP) and 7, 12-dimethylbenz(a)anthracene (DMBA). Unscheduled DNA synthesis was determined by measuring [methyl-3H]thymidine radioactivity incorporated into nuclear DNA of hepatocytes treated with carcinogens in the presence or absence of DHEA. Hydroxyurea $(5{\times}10^{-3} M)$was added to growth medium to selectively suppress normal replication. DHEA at concentrations ranging from $(1{\times}10^{-6} M)$ to$(5{\times}10^{-4} M)$ did not significantly inhibit unscheduled DNA synthesis induced by either MMS $(1{\times}10^{-4} M)$ or EMS $(1{\times}10^{-2} M)$. In contrast, DHEA-significantly inhibited unscheduled DNA synthesis induced by BaP $(6.5{\times}10^{-5} M)$ and DMBA.$(2{\times}10^{-5} M)$. DHEA-induced hepatotoxicity in rats was examined using lactate dehydrogenase (LDH) release as an indicator of cytotoxicity. DHEA exhibit no significant increase in LDH release compared with the control at 18 h. These data suggest that nontoxic concentration of DHEA does not affect the DNA excision repair process, but it probably influence the enzymatic system responsible for the metabolic activation of procarcinogens and thereby decreases the amount of the effective DNA adducts formed by the ultimate reactive carcinogenic species.

• Toxicological Research
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• 제31권3호
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• pp.265-271
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• 2015

This study was carried out to investigate contents of 8 polycyclic aromatic hydrocarbons (PAHs) from frequently consumed seafood and dairy products and to evaluate their chemical analysis methods. Samples were collected from markets of 9 cities in Korea chosen as the population reference and evaluated. The methodology involved saponification, extraction with n-hexane, clean-up on Sep-Pak silica cartridges and gas chromatograph-mass spectrometry analysis. Validation proceeded on 2 matrices. Recoveries for 8 PAHs ranged from 86.87 to 103.57%. The limit of detection (LOD) 8 PAHs was $0.04{\sim}0.20{\mu}g/kg$, and limit of quantification (LOQ) of 8 PAHs was $0.12{\sim}0.60{\mu}g/kg$. The mean concentration of benzo[a]pyrene (BaP) was $0.34{\mu}g/kg$ from seafood and $0.34{\mu}g/kg$ from dairy products. The total PAHs concentration was $1.06{\mu}g/kg$ in seafood and $1.52{\mu}g/kg$ in dairy products.

• 한국식품위생안전성학회지
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• 제19권4호
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• pp.176-184
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• 2004

PAHs 화합물은 유기탄소화합물의 불완전연소에 의해 주로 발생하는데, 일반인들은 대기오염에 의한 호흡노출과 가열조리식품의 경구섭취가 주요 인체노출경로로 알려지고 있다. 본 연구에서는 PAHs 화합물에 오염된 식품이 식생활에 많은 부분을 차지하고 있어 우리나라 대표식품을 참고로 가정식과 외식의 식단을 작성하고 작성한 식단을 근거로 식품 중 PAHs 화합물 오염도를 분석하여, 분석된 PAHs 화합물의 오염도 자료를 활용한 가정식과 외식 1끼 식사를 기준으로 인체노출량을 비교하고, 성인 하루 가정식 2회, 외식 1회 섭취시의 1일인체노출량을 평가하였다. 다빈도${\cdot}$다소비식품에서 PAHs 화합물 오염도를 분석한 결과 총 PAHs 농도는 $2.00\~141.28\;ug/kg$의 범위로 검출되었으며, 멸치볶음이 가장 높게 나타났다. 상대독성계수(TEFS)를 활용하여 환산한 독성등가량은 $0.03\~1.31\;ugTEQ_{BaP}/kg$ 범위였고, 가장 높은 값을 가진 식품은 햄버거이었다. 식품별 오염도와 노출변수들을 고려하여 산출한 끼니별 가정식과 외식에서의 PAHs 화합물 평균인체노출량은 각각 $2.4\times10^{-3}\;ugTEQ_{BaP}kg/meal$와 $4.0\times10^{-3}\;ugTEQ_{BaP}/kg/meal$으로 외식이 가정식보다 PAHs화합물의 인체노출이 1.7배가 높은 수준으로 나타났다 햄버거, 숯불쇠고기구이, 숯불삼겹살구이, 고등어구이 등은 PAHs화합물 오염도와 독성등가량 및 1회분식품섭취량이 모두 높아 PAHs화합물의 주요 노출기여식품인 것을 알 수 있었다. 가정식에서 미역국이 $1.8\times10^{-3}\;ugTEQ_{BaP}/kg/meal$으로, 외식에서는 햄버거가$3.0\times10^{-3}\;ugTEQ_{BaP}/kg/meal$으로 기여도가 가장 높았다. 하루 3회 식사를 고려한 1일 PAHs화합물인체노출량수준은 $8.0\times10^{-3}\~9.7\times10^{-3}\;ug/kg/day$이었다. 본 연구 결과가 PAHs 화합물의 안전성평가와 기준규격설정의 필요성 및 식품 안전관리를 위한 규제를 제정하는 기초 자료가 되길 바라며, PAHs 화합물의 고노출상황을 줄일 수 있는 개개인의 계획된 식단 작성시, 이에 대한 정보를 제공하고자 한다.

• Environmental Analysis Health and Toxicology
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• 제21권1호
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• pp.45-56
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• 2006

This study was conducted to investigate seasonal distributions of fine particles ($PM_{2.5}$) and associated polycyclic aromatic hydrocarbons (PAHs) at three cities. $PM_{2.5}$ samples were collected on glass fiber filters at urban (Chuncheon), metropolitan (Seoul), and industrial complex sites (Ulsan) from September, 2002 to February, 2004 using the Andersen FH 95 Particulate Sampler. About five 24-hour samples were collected from each site per season. The filters were analyzed for mass and six selected PAHs concentrations. $PM_{2.5}$ concentrations were the highest either in winter or spring, which could be attributed to the increase of fossil fuel combustion in winter or the transport of yellow sand to the Korean peninsula from China in spring, respectively. Regional $PM_{2.5}$ concentrations were higher in the order of Seoul>Chuncheon>Ulsan without statistical difference among cities. The filters were extracted using dichloromethane in an ultrasonicator and analyzed for six PAHs (anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, and benzo[a]pyrene) with HPLC. Total PAHs concentrations were statistically different among seasons in each site, and the highest concentrations were observed in winter at each sampling site. For total samples collected, the median total PAHs concentrations in Chuncheon ($4.6ng/m^3$) and Seoul ($4.4ng/m^3$) were approximately two times higher than that in Ulsan ($2.1ng/m^3$). Chrysene was a component found in the highest proportion among total PAHs at each site. Carcinogenic risks calculated based on the BaP toxic equivalency factors (TEFs) over the whole sampling period were higher in the order of Chuncheon>Seoul>Ulsan. This study suggests that the atmosphere of Chuncheon is contaminated with particulate matter and PAHs at the levels equivalent to those of Seoul and that an appropriate measure needs to be taken to mitigate human health risks from inhalation exposure to airborne fine particles.

• 한국환경과학회지
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• 제25권10호
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• pp.1349-1368
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• 2016

Concentrations of fine particulate matter ($PM_{2.5}$) and several of its particle constituents measured outside homes in Houston, Texas, and Los Angeles, California, were characterized using multiple regression analysis with proximity to point and mobile sources and meteorological factors as the independent variables. $PM_{2.5}$ mass and the concentrations of organic carbon (OC), elemental carbon (EC), benzo-[a]-pyrene (BaP), perylene (Per), benzo-[g,h,i]-perylene (BghiP), and coronene (Cor) were examined. Negative associations of wind speed with concentrations demonstrated the effect of dilution by high wind speed. Atmospheric stability increase was associated with concentration increase. Petrochemical source proximity was included in the EC model in Houston. Area source proximity was not selected for any of the $PM_{2.5}$ constituents' regression models. When the median values of the meteorological factors were used and the proximity to sources varied, the air concentrations calculated using the models for the eleven $PM_{2.5}$ constituents outside the homes closest to influential highways were 1.5-15.8 fold higher than those outside homes furthest from the highway emission sources. When the median distance to the sources was used in the models, the concentrations of the $PM_{2.5}$ constituents varied 2 to 82 fold, as the meteorological conditions varied over the observed range. We found different relationships between the two urban areas, illustrating the unique nature of urban sources and suggesting that localized sources need to be evaluated carefully to understand their potential contributions to $PM_{2.5}$ mass and its particle constituents concentrations near residences, which influence baseline indoor air concentrations and personal exposures. The results of this study could assist in the appropriate design of monitoring networks for community-level sampling and help improve the accuracy of exposure models linking emission sources with estimated pollutant concentrations at the residential level.

• Toxicological Research
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• 제33권4호
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• pp.265-272
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• 2017

Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP), acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form bulky DNA adducts when absorbed by mammalian cells. These chemicals are metabolically activated to reactive forms in mammalian cells and preferentially get attached covalently to the $N^2$ or C8 positions of guanine or the $N^6$ position of adenine. The proportion of $N^2$ and C8 guanine adducts in DNA differs among chemicals. Although these adducts block DNA replication, cells have a mechanism allowing to continue replication by bypassing these adducts: translesion DNA synthesis (TLS). TLS is performed by translesion DNA polymerases-Pol ${\eta}$, ${\kappa}$, ${\iota}$, and ${\zeta}$ and Rev1-in an error-free or error-prone manner. Regarding the NBA adducts, namely, 2-(2'-deoxyguanosin-$N^2$-yl)-3-aminobenzanthrone (dG-$N^2$-ABA) and N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-ABA), dG-$N^2$-ABA is produced more often than dG-C8-ABA, whereas dG-C8-ABA blocks DNA replication more strongly than dG-$N^2$-ABA. dG-$N^2$-ABA allows for a less error-prone bypass than dG-C8-ABA does. Pol ${\eta}$ and ${\kappa}$ are stronger contributors to TLS over dG-C8-ABA, and Pol ${\kappa}$ bypasses dG-C8-ABA in an error-prone manner. TLS efficiency and error-proneness are affected by the sequences surrounding the adduct, as demonstrated in our previous study on an ABP adduct, N-(2'-deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-ABP). Elucidation of the general mechanisms determining efficiency, error-proneness, and the polymerases involved in TLS over various adducts is the next step in the research on TLS. These TLS studies will clarify the mechanisms underlying aryl hydrocarbon mutagenesis and carcinogenesis in more detail.