• Title/Summary/Keyword: BaP(benzo(a)pyrene)

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Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer-

  • Das, Jayeeta;Samadder, Asmita;Das, Sreemanti;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.19 no.1
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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.

Characteristics of Hazardous Air Pollutants in the Steel Industrial City, Pohang ( I ) - Polycyclic Aromatic Hydrocarbons (철강산업도시 포항지역 유해대기오염물질의 오염특성 ( I ) - 다환방향족탄화수소)

  • Baek, Kyung-Min;Seo, Young-Kyo;Cho, Byoung-Yoon;Baek, Sung-Ok
    • Journal of Korean Society for Atmospheric Environment
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    • v.34 no.2
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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.

Stress Expression by the Maternally Transferred Xenobiotic Pollutants in the Reproductive Outputs of the Pacific Oyster, Crassostrea gigas

  • Jo, Qtae;Choy, Eun-Jung;Lee, Su-Jeong;Cho, Yong-Chul;Lee, Chu;Kim, Yoon
    • Journal of Aquaculture
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    • v.18 no.3
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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.

Trend and policy directions of primary carbonaceous aerosols in Seoul (서울의 일차탄소성분 입자 농도 변화 및 관리 방향)

  • Eunlak Choi;Ji Yi Lee;Yong Pyo Kim
    • Particle and aerosol research
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    • v.20 no.1
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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.

Modulation of Chemical Carcinogen-Induced Unscheduled DNA Synthesis by Dehydroepiandrosterone (DHEA) in the Primary Rat Hepatocytes

  • Kim, Seung-Hee;Han, Hyung-Mee;Kang, Seog-Youn;Jung, Ki-Kyung;Kim, Tae-Gyun;Oh, Hye-Young;Lee, Young-Kyung;Rheu, Hang-Mook
    • Archives of Pharmacal Research
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    • v.22 no.5
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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.

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Evaluation of Chemical Analysis Method and Determination of Polycyclic Aromatic Hydrocarbons Content from Seafood and Dairy Products

  • Lee, So-Young;Lee, Jee-Yeon;Shin, Han-Seung
    • Toxicological Research
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    • v.31 no.3
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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.

Exposure Assessment for Polycyclic Aromatic Hydrocarbons in the Model Menu System of Korean (한국인의 모델식이에 대한 다환방향족탄화수소류(PAHs)의 인체노출량평가)

  • Kim YunHee;Yoon EunKyung;Lee HyoMin;Park KyungAh;Jun EunAh;Lee CherlHo;Choi SangYun;Lim SeungTaek;Ze KeumRyun;Choi KwangSik
    • Journal of Food Hygiene and Safety
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    • v.19 no.4
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    • pp.176-184
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    • 2004
  • This study was conducted to compare and estimate the daily PAHs dietary intake from both home-cooking and dining-out, through approach of model diet used in exposure assessment of food contaminants. Food commodities reflecting in model diet were selected from the KHIDI report and were analysed in cooked or uncooked edible forms using HPLC-Fluorscence Detector. The PAHs dietary intake comparison between home-cooking and dining-out was based on one meal intake suggested in model diet and PAHs dietary intake was estimated by using food consumption rate and body weight of the Korean adult group. The daily PAHs dietary intake was calculated by permutation and combination method with assumption that a person consumed 2 meals from home-cooking menu and 1 meal from dining-out menu. The total PAHs levels in 36 food commodities with 200 samples were ranged from 2.00 ug/kg to 141.28 ug/kg and a food showing the highest PAHs level was the stir-fried anchovy. The $TEQ_{BaP}$ levels of PAHs were calculated using benzo(a)pyrene equivalents individual congener level and corresponding TEF value and the $TEQ_{BaP}$ level were ranged from $0.03\;ugTEQ{BaP}$ to $1.31\;ugTEQ_{BaP}$ and a food showing the highest $TEQ_{BaP}$ level was the hamburger. The PAHs dietary intakes per one meal from home-cooking and dining-out were $2.4\times10^{-3}\;ugTEQ_{BaP}/kg/meal\;and\;4.0\times10^{-3}\;ugTEQ_{BaP}/kg/meal$, respectively. This data showed the PAHs dietary intake from dining-out was about 1.7 times higher than from the home-cooking. The daily PAHs dietary intakes of general Korean adult having two meals from home-cooking and one meal from dining-out per a day were ranged between $8.0\times10^{-3}\~9.7\times10^{-3}\;ugTEQ_{BaP}/gg/day$ and mean value as $8.9\times10^{-3}\~9.7\times10^{-3}\;ugTEQ_{BaP}/gg/day$.

Characteristics of Seasonal Distributions of Fine Particles ($PM_{2.5}$) and Particle-Associated Polycyclic Aromatic Hydrocarbons in Urban, Metropolitan and Industrial Complex Sites (중소도시, 대도시 및 산업지역에서 채취한 미세분진 ($PM_{2.5}$)과 입자상 다환방향족탄화수소의 계절적인 분포 특성)

  • Kim He-Kap;Jung Kyung-Mi;Kim Tae-Sik
    • Environmental Analysis Health and Toxicology
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    • v.21 no.1 s.52
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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.

Source Proximity and Meteorological Effects on Residential Ambient Concentrations of PM2.5, Organic Carbon, Elemental Carbon, and p-PAHs in Houston and Los Angeles, USA

  • Kwon, Jaymin;Weisel, Clifford P.;Morandi, Maria T.;Stock, Thomas H.;Turpin, Barbara
    • Journal of Environmental Science International
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    • v.25 no.10
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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.

Error-Prone and Error-Free Translesion DNA Synthesis over Site-Specifically Created DNA Adducts of Aryl Hydrocarbons (3-Nitrobenzanthrone and 4-Aminobiphenyl)

  • Yagi, kashi;Fujikawa, Yoshihiro;Sawai, Tomoko;Takamura-Enya, Takeji;Ito-Harashima, Sayoko;Kawanishi, Masanobu
    • Toxicological Research
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    • v.33 no.4
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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.