• 제목/요약/키워드: Adduct Formation

검색결과 85건 처리시간 0.024초

에틸렌옥사이드에 폭로된 흰쥐의 혈액에 형성된 헤모글로빈 부가체에 대한 연구 (A Study on Formation of Hemoglobin Adduct in Blood of Mice Inhaled with Ethylene Oxide)

  • 이진헌;신호상;안혜실
    • 한국환경보건학회지
    • /
    • 제32권2호
    • /
    • pp.164-170
    • /
    • 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.

Accelerated DNA Adduct Formation in the Lung of the Nrf2 Knockout Mouse Exposed to Diesel Exhaust

  • Aoki, Yasunobu;Sato, Hiromi;Nishimura, Noriko;Takahashi, Satoru;Itoh, Ken;Yamamoto, Masayuki
    • 한국환경성돌연변이발암원학회:학술대회논문집
    • /
    • 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
    • /
    • pp.36-42
    • /
    • 2002
  • Diesel exhaust (DE) has been recognized as a noxious mutagen and/or carcinogen, because its components can form DNA adducts. Mechanisms governing the susceptibility to DE and the efficiency of such DNA adduct formation require clarification. The transcription factor Nrf2 is essential for inducible and/or constitutive expression of a group of detoxification and antioxidant enzymes, and we hypothesized that the nrf2 gene knockout mouse might serve as an excellent model system for analyzing DE toxicity. To address this hypothesis, lungs from nrf2(-/-) and nrf2(+/-) mice were examined for the production of xenobiotic-DNA adducts after exposure to DE (3 $mg/m^{3}$ suspended particulate matter) for 4 weeks. Whereas the relative adduct levels (RAL) were significantly increased in the lungs of both nrf2(+/-) and nrf2(-/-) mice upon exposure to DE, the increase of RAL in the lungs from nrf2(-/-) mice exposed to DE were approximately 2.3-fold higher than that of nrf2(+/-) mite exposed to DE. In contrail, cytochrome P4501Al mRNA levels in the nrf2(-/-)mouse lungs were similar to those in the nrf2(+/-) mouse lungs even after exposure to DE, suggesting that suppressed activity of phase II drug-metabolizing enzymes is important in giving ise to the increased level of DNA adducts in the Nrf2-null mutant mouse subjected to DE. Importantly, severe hyperplasia and accumulation of the oxidative DNA adduct 8-hydroxydeoxyguanosine were observed in the bronchial epidermis of nrf(-/-) mite following DE exposure. These results demonstrate the increased susceptibility of the nrf2 germ line mutant mouse to DE exposure and indicate the nrf2 gene knockout mouse nay represent a valuable model for the assessment of respiratory DE toxicity.

  • PDF

In vitro에서 발암물질에 의한 발암진행에 미치는 천궁약침액의 영향 (Effect of Cnidium officinale Makino Aqua-acupuncture Solution on Carcinogen-induced Carcinogenesis in In vitro)

  • 한상훈;노동일;이기택;손윤희;백태선;남경수;임종국
    • Korean Journal of Acupuncture
    • /
    • 제19권1호
    • /
    • pp.7-13
    • /
    • 2002
  • 1. 천궁약침액은 1${\times}$에서 15.1%의 cytochrome P4501A1 저해효과를 나타냈으며 그 억제효과는 약침액의 농도가 높을수록 증가하였다. 2 천궁약침액은 benzo[a]pyrene과 세포의 DNA 결합을 유의성있게 억제시켰다. 이상의 결과를 종합해 볼때 천궁약침액은 효과적으로 cytochrome P4501A1 효소를 저해했으며, 발암물질과 DNA의 결합을 억제시켜 외부 물질 또는 대사물에 의해 일어날 수 있는 돌연변이와 암 발생을 억제할 것으로 사료된다.

  • PDF

어유 지방산과 요소의 부가화합물 형성을 이용한 EPA와 DHA의 선택적 농축방법 (Selective Enrichment of EPA end DHA by Adduct Formation of Folly Acids of Fish Oil and Urea)

  • 한대석;안병학;신현경
    • 한국식품과학회지
    • /
    • 제22권5호
    • /
    • pp.520-525
    • /
    • 1990
  • 포화지방산 또는 불포화지방산의 분리방법인 요소부 가법이 지닌 가메탄올 분해(methanolysis)와 농축물 회수의 곤란함 등의 문제를 해결하기 위하여 지방산과 요소의 부가화합물 형성의 반응매질로 유기용매를 사용하고 요소의 습윤제로 물을 사용한 새로운 요소부가법을 제시하였다. 어유를 원료로 제조한 지방산을 헵탄, 헥산, 이소옥탄같은 비극성 유기용매에 용해키시고 요소와 요소의 습윤제인 물을 첨가하여 부가화합물 형성을 유도한 후 요소와 부가화합물을 잘 형성하지 않는 불포화지방산 분획을 회수하여 지방산 조성을 분석한 결과 EPA, DHA 및 이들의 전구물질을 포함한 고도불포화지방산이 80%이상인 것으로 나타났다. 이 고도불포화지방산 농축물내에 EPA와 DHA 함량은 사용하는 유기용매으 종류에 따라서 변화되었는데, 헵탄과 에틸 에테르 등을 사용할 경우에는 EPA의 농축에 효과가 높았다. 이러한 특성을 이용하여 우선 펜탄을 사용하여 DHA를 농축하고 다시 헵탄을 사용하여 EPA의 농축을 시도한 바 어유 지방산으로부터 DHA가 50%인 농축물과 EPA가 53%인 분획을 각각 얻을 수 있었다.

  • PDF

Synthesis, Characterization and in Vitro Identification of $N^7-Guanine$ Adduct of 2-Bromopropane

  • Zhao, Long-Xuan;Kim, Eun-Kyung;Lim, Hyun-Tae;Moon, Yoon-Soo;Kim, Nam-Hee;Kim, Tae-Hyung;Choi, Heesung;Chae, Whigun;Jeong, Tae-Cheon;Lee, Eung-Seok
    • Archives of Pharmacal Research
    • /
    • 제25권1호
    • /
    • pp.39-44
    • /
    • 2002
  • Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2i-deoxyguanosine abduct formation by 2- bromopropane was investigated in vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression. $N^7-Guanine adduct$ of 2'-bromopropane (i.e., $N^7-isopropyl$ guanine) was chemically synthesized and structurally characterized by analysis of UV,$^1H-NMR,{\;}^{13}C-NMR$, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2'-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at $37^{\circ}C$ for 16 h, followed by a thermal hydrolysis, produced a detectable amount of $N^7-isopropyl$ guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct in $N^7-position$ of 2'-deoxyguanosine at 3 Physiological condition.

댑싸리하고초(夏枯草) 약침액(藥鍼液)의 암예방 활성 (Chemopreventive activity of Prunella Herba Vulgaris L. Aqua-acupuncture Solution)

  • 박신화;임종국
    • Korean Journal of Acupuncture
    • /
    • 제18권1호
    • /
    • pp.11-20
    • /
    • 2001
  • 댑싸리하고초 약침액을 이용하여 phase II detoxification 효소인 quinone reductase (QR 및 GST) 유도, GSH 생성량, phase I 효소 cytochrome P4501A1 활성억제, 발암물질 B[a]P-DNA adduct 형성의 저해효과 등을 측정하였다. QR 생성 유도를 Hepa1c1c7로 실험한 결과, 댑싸리하고초 약침액및 열수추출액 모두에서 유도 되었으며, 농도가 높아질수록 유도율이 더 높게 나타났으며, GSH와 GST의 유도율도 약침액에서 나타났다. 댑싸리하고초 약침액 $5{\times}$에서 45.2%의 cytochrome P4501A1 효소활성 저해효과를 측정할 수 있었다. 또한 B[a]P-DNA binding 저해효과를 실험한 결과, 약침액 $3{\times}$ 농도에서 45.0%의 저해효과가 있었다. 이상의 결과에 의하면 댑싸리하고초 약침액은 암억제 물질로서의 기능을 충분히 발휘할 것으로 사료된다.

  • PDF

Synergistic extraction of lanthanoids(III) with thenoyltrifluoroacetone and aromatic carboxylic acids and the hydration of the extracted species

  • Ishiwata, E.;Kimura, T.;Kato, Y.;Hasegawa, Y.
    • 분석과학
    • /
    • 제8권4호
    • /
    • pp.499-503
    • /
    • 1995
  • In order to study how and why the stabilities of lanthanoid(III) complexes in solutions vary across the series, the formation constants of the adducts of tris(2-thenoyltrifluoroacetonato)lanthanoids(III) with seven carboxylic acids in chloroform have been determined by solvent extraction technique at 298K. The formation constants with carboxylic acids generally decrease with increasing the atomic number, but in the middle of the series, they change only slightly. Such trends have been interpreted as related to a change of the coordination number in the middle of the series. It has been attempted to determine the number of water molecules coordinated to the adducts as well as $Eu(TTA)_3$ in chloroform by measuring the fluorescence life time of europium(III), to ensure the assignment of the coordination number.

  • PDF

Ginseng Prevents DNA-adduct Formation in Rat Hepatocytes in vitro Treated with DMBA

  • Kumar, Ashok
    • 고려인삼학회:학술대회논문집
    • /
    • 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
    • /
    • pp.263-269
    • /
    • 1998
  • It is an established fact that most of the carcinogens implicate bay-region diol epoxides as the ultimate carcinogenic metabolites. These electrophiles react with nucleophilic sites in the cells to form abducts. It is the formation of carcinogenic-DNA adducts that is thought to initiate carcinogenesis. In our previous study we have reported chemopreventive property of Ginseng on 7,12-dimethylbenz (a)anthracene (DMBA) induced skin papillomagenesis in male Swiss albino mice. In this study we have examined the effect on formation of DMBA-DNA adducts in rat hepatocytes pretreated with ginseng. Primary cultures of rat hepatocytes were used. The cells wets treated with ginseng for 24 hrs and then with DMBA (iOn) for 18 hrs. Cells were then harvested, their DNA was isolated and analyzed by P)2 labelling. A significant reduction in the levels of DMBA-DNA adduces (adducts/108 nucleotides) was observed in all cultures pretreated with ginseng. The viability of cells was not affected by pre-treatment with ginseng. Our finding suggests that ginseng block or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogens.

  • PDF