본문 바로가기
HOME> 저널/프로시딩 > 저널/프로시딩 검색상세

저널/프로시딩 상세정보

권호별목차 / 소장처보기

H : 소장처정보

T : 목차정보

Biochemical pharmacology 18건

  1. [해외논문]   Potential role of environmental genotoxic agents in diabetes mellitus and neurodegenerative diseases  

    Eizirik, Décio L. ; Spencer, Peter ; Kisby, Glen E.
    Biochemical pharmacology v.51 no.12 ,pp. 1585 - 1591 , 1996 , 0006-2952 ,

    초록

    Abstract Epidemiological data suggest that environmental genotoxins are risk factors for some forms of diabetes mellitus and neurodegenerative diseases. The present commentary focuses on mechanisms involved in genotoxin-induced pancreatic β-cell and neuronal damage. These two cell types seem to share a similar vulnerability to different forms of DNA damage, and the long-term consequences of repeated genotoxic insults to post-mitotic neurons or slowly proliferating β-cells remain to be clarified. One intriguing possibility is that genotoxins could act as “slow” toxins in these cells, triggering a cascade of cellular events, which culminates in progressive cell dysfunction and loss. Indeed, exposure to mutagenic nitroso agents such as streptozotocin and cycasin induces long-lasting damage to both β-cells and neurons. These data on cycasin, a toxin obtained from the cycad plant ( Cycas spp.), are of special interest, since this agent may be implicated in both amyotrophic lateral sclerosis/Parkinson dementia complex and diabetes mellitus in the western Pacific area. Future studies are required to sort out the interactions between different genotoxic agents, viral infections, and cellular repair mechanisms on cellular survival and function. Moreover, further epidemiological studies are needed to clarify the role of N -nitrosoureas in diabetes mellitus and neurodegenerative diseases in populations with different genetic backgrounds. Answers to these questions may provide useful information on the pathogenesis of these devastating diseases, and open the possibility for their primary prevention.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  2. [해외논문]   Nitric oxide (NO•), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase  

    Dierks, Elizabeth A. ; Burstyn, Judith N.
    Biochemical pharmacology v.51 no.12 ,pp. 1593 - 1600 , 1996 , 0006-2952 ,

    초록

    Abstract In the present study, we determined that of the redox forms of nitrogen monoxide, NO − , NO • and NO + , only NO . significantly activates soluble guanylyl cyclase (GTP pyrophosphate-lyase cyclizing, EC 4.6.1.2). Neither of the NO − donors tested, Angeli's salt (Na 2 N 2 O 3 ) or Piloty's acid (C 6 H 5 SO 2 NHOH), caused a change in the guanylyl cyclase activity relative to the basal activity level. Interference by other reaction products was eliminated as a possible explanation for the lack of activation. To the extent that NO + could be stabilized in aqueous solution, by dissolution of the nitrosonium salt NOPF 6 in dry organic solvent prior to addition to the enzyme in buffer, NO + had no effect on the activity of soluble guanylyl cyclase. The counter-ion, PF 6 − , had a minimal effect on the enzyme activity and, therefore was, not responsible for the lack of activation by NO + . These observations suggest that NO . is the natural activator of soluble guanylyl cyclase and is reasonably identical with endothelium-derived relaxing factor, the physiological regulator of soluble guanylyl cyclase activity.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  3. [해외논문]   5-(m-Benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-tri-o-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration : Implications for chemotherapy  

    Ashour, Osama M. ; Naguib, Fardos N.M. ; el Kouni, Mahmoud H.
    Biochemical pharmacology v.51 no.12 ,pp. 1601 - 1611 , 1996 , 0006-2952 ,

    초록

    Abstract 5-( m -Benzyloxybenzyl)barbituric acid acyclonucleoside (BBBA), the most potent inhibitor known of uridine phosphorylase (UrdPase, EC 2.4.2.3), the enzyme responsible for uridine catabolism, and 2′,3′,5′-tri- O -acetyluridine (TAU), a prodrug of uridine, were used to investigate the possibility of improving the bioavailability of oral uridine in mice. Oral BBBA administered at 30, 60, 120, and 240 mg/kg increased the concentration of plasma uridine (2.6 ± 0.7 μM) by 3.2-, 4.6-, 5.4-, and 7.2-fold, respectively. After administration of 120 and 240 mg/kg BBBA, plasma uridine concentration remained 3- and 6-fold, respectively, higher than the plasma concentration at zero time (C 0 ) for over 8 hr. On the other hand, BBBA did not change the concentration of plasma uracil. TAU was far more superior than uridine in improving the bioavailability of plasma uridine. The relative bioavailability of plasma uridine released from oral TAU (53%) was 7-fold higher than that (7.7%) obtained by oral uridine. Oral TAU at 460, 1000, and 2000 mg/kg achieved area under the curve ( AUC ) values of plasma uridine of 82, 288, and 754 μmol · hr/L, respectively. Coadministration of BBBA with uridine or TAU further improved the bioavailability of plasma uridine resulting from the administration of either alone and reduced the C max and AUC of plasma uracil. Coadministration of BBBA at 30, 60, and 120 mg/kg improved the relative bioavailability of uridine released from 2000 mg/kg TAU (53%) by 1.7-, 2.7-, and 3.9-fold, respectively, while Coadministration of the same doses of BBBA with an equimolar dose of uridine (1320 mg/kg) increased the relative bioavailability of oral uridine (7.7%) by 4.1-, 5.3-, and 7.8-fold, respectively. Moreover, the AUC and C max of plasma uridine after BBBA (120 mg/kg) Coadministration with TAU were 3.5-and 11.5-fold, respectively, higher than those obtained from Coadministration of BBBA with an equimolar dose of uridine. The exceptional effectiveness of the BBBA plus TAU combination in elevating and sustaining high plasma uridine concentration can be useful in the management of medical disorders that are remedied by administration of uridine as well as to rescue or protect from host-toxicities of various chemotherapeutic pyrimidine analogues.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  4. [해외논문]   Effects of propofol and thiopentone on potassium- and carbachol-evoked [3H]noradrenaline release and increased [Ca2+]i from SH-SY5Y human neuroblastoma cells  

    Lambert, David G. ; Willets, Jonathon M. ; Atcheson, Robert ; Frost, Christine ; Smart, Darren ; Rowbotham, David J. ; Smith, Graham
    Biochemical pharmacology v.51 no.12 ,pp. 1613 - 1621 , 1996 , 0006-2952 ,

    초록

    Abstract We have examined the effects of two intravenous anaesthetic induction agents, propofol and thiopentone, on K + and carbachol evoked [ 3 H]noradrenaline release from a human neuroblastoma cell line, SH-SY5Y. In this model, we have previously demonstrated that K + evoked [ 3 H]noradrenaline release was dependent on Ca 2+ entry and carbachol evoked release was extracellular Ca 2+ -independent. Propofol inhibited K + (100 mM)-evoked ( IC 50 of 42 ± 11 μM), but not carbachol (1 mM)-evoked, [ 3 H]noradrenaline release. Thiopentone inhibited both K + - and carbachol-evoked release with IC 50 values of 116 ± 15 μM and 169 ± 39 μM, respectively. These inhibitory effects were not due to changes in the release dynamics, as assessed using perfused cells. Furthermore, thiopentone inhibition of carbachol-evoked release was not due to muscarinic receptor antagonism. Both propofol and thiopentone caused noncompetitive inhibition of K + -stimulated Ca 2+ influx, with IC 50 values of 127 ± 7 μM and 121 ± 10 μM, respectively. These effects were not due to interaction with GABA A receptors, but suggest that both compounds block voltage-sensitive Ca 2+ channels. Thiopentone, but not propofol, inhibited carbachol-stimulated increased intracellular Ca 2+ concentrations in the presence and absence of extracellular Ca 2+ . However, thiopentone had no effect on carbachol-stimulated inositol (1,4,5)-triphosphate formation, suggesting that thiopentone may directly inhibit Ca 2+ release from intracellular stores.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  5. [해외논문]   Enzymology of mitomycin C metabolic activation in tumour tissue : Characterization of a novel mitochondrial reductase  

    Spanswick, Victoria J. ; Cummings, Jeffrey ; Smyth, John F.
    Biochemical pharmacology v.51 no.12 ,pp. 1623 - 1630 , 1996 , 0006-2952 ,

    초록

    Abstract In this study, the enzymology of mitomycin C (MMC) bioactivation in two murine colon adenocarcinomas, MAC 16 and MAC 26, was examined. Subcellular quinone reductase assessment via cytochrome c reduction confirmed a number of active enzymes. MAC 16 exhibited 22-fold greater levels of cytosolic DT-diaphorase than MAC 26, while microsomal NADPH:cytochrome P-450 reductase levels were similar in both tumour types. Metabolism of MMC by subcellular fractions isolated from both MAC 16 and MAC 26 was quantitated by monitoring the formation of the principle metabolite 2,7-diaminomitosene (2,7-DM) via high-performance liquid chromatography (HPLC). In MAC 16 only, activity displaying the properties of cytosolic DT-diaphorase and microsomal NADPH:cytochrome P-450 reductase was detected and confirmed, using the enzyme inhibitors dicoumarol and cytochrome P-450 reductase antiserum, respectively. The highest level of MMC metabolism was associated with the mitochondrial fraction from both tumours and was the sole enzyme activity detected in MAC 26. The greatest mitochondrial drug metabolism was achieved in the presence of NADPH as cofactor and hypoxia (MAC 16-specific activity, 3.67 ± 0.58 nmol/30 min/mg; MAC 26 specific-activity, 3.87 ± 0.71 nmol/30 min/mg) and was unaffected by the addition of the inhibitors dicoumarol and cytochrome P-450 reductase antiserum. NADH-dependent mitochondrial activity was only observed in MAC 16 at approximately 4-fold less than that seen with NADPH. MAC 26 homogenate incubations displayed enhanced metabolism under hypoxia, presumably due to the presence of the identified mitochondrial enzyme. MAC 16 homogenates showed no increase in metabolism under hypoxia, suggesting that other enzyme(s) may be predominant. These data indicate the presence of a novel mitochondrial one-electron reductase capable of metabolising MMC in MAC 16 and MAC 26.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  6. [해외논문]   In vitro characterization of a novel series of platelet-derived growth factor receptor tyrosine kinase inhibitors  

    Sawutz, David G. ; Bode, Donald C. ; Briggs, G.Maurice ; Reid, John R. ; Canniff, Paul ; Caldwell, Lisa ; Faltynek, Connie R. ; Miller, Deborah ; Dunn, Joseph A. ; de Garavilla, Lawrence ; Guiles, Joseph W. ; Weigelt, Carolyn ; Michne, William ; Treasurywala, Adi M. ; Silver, Paul J.
    Biochemical pharmacology v.51 no.12 ,pp. 1631 - 1638 , 1996 , 0006-2952 ,

    초록

    Abstract In this report, we describe the discovery and characterization of a novel biarylhydrazone series of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors typified by the prototype WIN 41662 (3-phenyl- N 1 -[1-(4-pyridyl)pyrimidine]hydrazone). WIN 41662 inhibited PDGF-stimulated autophosphorylation of PDGF receptors from human vascular smooth muscle cells (hVSMC) with an IC 50 value of 60 nM. The inhibitor appeared to be competitive with respect to substrate (Mn 2+ -ATP), having a calculated K i of 15 ± 5 nM. WIN 41662 was approximately 500-fold more potent in inhibiting the PDGF receptor tyrosine kinase than the p56 lck tyrosine kinase. It was inactive against other serine/threonine and tyrosine kinases tested. WIN 41662 produced concentration-dependent inhibition of PDGF-stimulated receptor autophosphorylation in intact hVSMC with an IC 50 2+ mobilization and cell proliferation were events that occurred in hVSMC subsequent to PDGF receptor activation. WIN 41662 inhibited PDGF-stimulated Ca 2+ mobilization and cell proliferation ([ 3 H]TdR incorporation) with IC 50 values of 430 nM and 2.3 μM, respectively. These effects appeared to be specifically related to PDGF receptor tyrosine kinase inhibition since WIN 41662 was not cytotoxic ( in vitro ) and since WIN 72039, a close structural analog that does not inhibit PDGF receptor tyrosine kinase, also did not inhibit PDGF-stimulated receptor autophosphorylation, Ca 2+ mobilization, or hVSMC proliferation. Thus, WIN 41662 is representative of a novel class of selective PDGF receptor tyrosine kinase inhibitors that inhibit PDGF-regulated secondary events in intact cells.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  7. [해외논문]   Characterization of the catecholamine extraneuronal uptake2 carrier in human glioma cell lines SK-MG-1 and SKI-1 in relation to (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) selective cytotoxicity  

    Noë, Adrian J. ; Marcantonio, Daniela ; Barton, James ; Malapetsa, Areti ; Panasci, Lawrence C.
    Biochemical pharmacology v.51 no.12 ,pp. 1639 - 1648 , 1996 , 0006-2952 ,

    초록

    Abstract Transport of (2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) and (−)-norepinephrine was investigated in SarCNU-sensitive SK-MG-1 and -resistant SKI-1 human glioma cell lines. [ 3 H]SarCNU influx was inhibited by SarCNU, sarcosinamide, and (±)-epinephrine in SK-MG-1 cells with competitive inhibition observed by (±)-epinephrine ( K i = 140 ± 12 μM) and (±)-norepinephrine ( K i = 255 ± 41 μM). No effect on influx was detected in SKI-1 cells. [ 3 H](-)-Norepinephrine influx was linear to 15 sec in both cell lines and temperature dependent only in SK-MG-1 cells. Influx of [ 3 H](−)-norepinephrine was found to be saturable in SK-MG-1 ( K m = 148 ± 28 μM, V max = 1 1.23 ± 0.18 pmol/μL intracellular water/sec) but not in SKI-1 cells. In SK-MG-1 cells, [ 3 H](−)-norepinephrine influx was found to be inhibited competitively by (−)-epinephrine ( K i = 111 ± 7 μM) and SarCNU ( K i = 1.48 ± 0.22 mM). Ouabain and KCl were able to inhibit the [ 3 H](−)-norepinephrine influx in SK-MG-1 cells, consistent with influx being driven by membrane potential. Several catecholamine uptake 2 inhibitors were able to reduce significantly the influx of [ 3 H](−)-norepinephrine and [ 3 H]SarCNU with no inhibition by a catecholamine uptake 1 inhibitor. These findings suggest that increased sensitivity of SK-MG-1 to SarCNU is secondary to enhanced accumulation of SarCNU mediated via the catecholamine extraneuronal uptake 2 transporter, which is not detectable in SKI-1 cells. The introduction of SarCNU into clinical trials will confirm if increased uptake via the catecholamine extraneuronal uptake 2 transporter will result in increased antitumor activity.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  8. [해외논문]   Cytotoxicity and DNA damage associated with pyrazoloacridine in MCF-7 breast cancer cells  

    Grem, Jean L. ; Politi, Pedro M. ; Berg, Stacey L. ; Benchekroun, Nabil M. ; Patel, Mahendra ; Balis, Frank M. ; Sinha, Birandra K. ; Dahut, William ; Allegra, Carmen J.
    Biochemical pharmacology v.51 no.12 ,pp. 1649 - 1659 , 1996 , 0006-2952 ,

    초록

    Abstract We examined the effects of pyrazoloacridine (PZA), an investigational anticancer agent in clinical trials, on cytotoxicity, DNA synthesis, and DNA damage in MCF-7 human breast carcinoma cells. With PZA concentrations ranging from 0.5 to 50 μM for durations of 3–72 hr, cytotoxicity increased in proportion to the total PZA exposure (concentration × time). Inhibition of DNA and RNA syntheses increased with increasing PZA concentration x time (μM · hr). A 24-hr exposure to 1 and 10 μM PZA reduced DNA synthesis to 62 and 5% of control, respectively, decreased the proportion of cells in S phase with accumulation of cells in G 2 + M phase, and inhibited cell growth at 72 hr by 68 and 100%. Newly synthesized DNA was more susceptible to damage during PZA exposure, with subsequent induction of parental DNA damage. Significant damage to newly synthesized DNA as monitored by alkaline elution was evident after a 3-hr exposure to ⩾5 μM PZA. Longer PZA exposures (⩾10 μM for 16 hr) were required to elicit damage to parental DNA. Induction of single-strand breaks in parental DNA correlated closely with induction of double-strand breaks and detachment of cells from the monolayer. PZA-mediated DNA fragmentation was not accompanied by the generation of oligonucleosomal laddering in MCF-7 cells, but induction of very high molecular weight DNA fragmentation (0.5 to 1 Mb) was detected by pulsed-field gel electrophoresis. In vitro binding of PZA to linear duplex DNA (1 kb DNA ladder) and closed, circular plasmid DNA was demonstrated by a shift in migration during agarose electophoresis. PZA interfered with topoisomerase I- and II-mediated relaxation of plasmid DNA in a cell-free system, but the cytotoxic effects of PZA did not appear to involve a direct interaction with topoisomerase I or II (stabilization of the topoisomerase I- or II-DNA cleavable complex). PZA-mediated cytotoxicity correlated strongly with inhibition of DNA and RNA syntheses, and damage to both nascent and parental DNA. Neither the cytotoxicity of PZA nor induction of double-stranded DNA fragmentation was prevented by aphidicolin, indicating that PZA-mediated lethality occurred in the absence of DNA replication. Since free radical formation was not detected, induction of nascent and parental DNA damage appeared to be a consequence of the avid binding of PZA to DNA, presumably by interfering with the access of replication, repair, and transcription enzyme complexes.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  9. [해외논문]   Arylacetamide deacetylase activity towards monoacetyldapsone : Species comparison, factors that influence activity, and comparison with 2-acetylaminofluorene and p-nitrophenyl acetate hydrolysis  

    Preuss, Charles V. ; Svensson, Craig K.
    Biochemical pharmacology v.51 no.12 ,pp. 1661 - 1668 , 1996 , 0006-2952 ,

    초록

    Abstract The deacetylation of monoacetyldapsone (MADDS) was examined in liver microsomes and cytosol from male Sprague-Dawley rats, Golden Syrian hamsters, and Swiss Albino mice. All three rodent species demonstrated greater MADDS deacetylation activity in liver microsomes than in liver cytosol. Further investigations were conducted in hamsters. The velocity of MADDS deacetylation in major organs in the hamster was greatest in the intestine, followed by the liver and kidney. The effect of pretreatment with common inducers on liver microsomal deacetylation activity was also examined in the hamster. Phenobarbital, 100 mg/kg/day × 3 days, did not alter activity, while dexamethasone at the same dose reduced 2-acetylaminofluorene (2-AFF), MADDS, and p -nitrophenyl acetate (NPA) hydrolysis by at least 50%. Due to a previous report that KI activated the deacetylation of an arylacetamide in vitro (Khanna et al ., J Pharmacol Exp Ther 262 : 1225–1231, 1992), the effects of the halides KF, KCl, KBr and KI on MADDS hydrolysis in vitro were tested. Of the halides studied, only KF altered MADDS hydrolysis, resulting in an almost complete inhibition of deacetylase activity at 50 mM (with the initial concentration of MADDS at 0.6 mM) with an IC 50 = 0.16 mM. Cornish-Bowden and Dixon plots indicated that the inhibition exerted by KF was non-competitive. The rank order of inhibitor potencies was constructed using phenylmethylsulfonyl fluoride (PMSF), bis ( p -nitrophenyl)phosphate (BNPP), physostigmine, and KF with 2-AFF, MADDS, and NPA as substrates. Different rank order potencies were obtained for each of the substrates tested. The substrates 2-AFF, MADDS, and NPA did not act as competitive inhibitors on the hydrolysis rates of each other. Liver microsomal arylacetamide deacetylase activity was greater in male hamsters than in females with either MADDS or 2-AAF as substrates; however, hydrolysis of NPA was similar in both male and female hamsters. These data support the hypothesis that the enzyme which catalyzes the hydrolysis of MADDS differs from that catalyzing either 2-AAF or NPA hydrolysis.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지
  10. [해외논문]   Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase  

    Belcourt, Michael F. ; Hodnick, William F. ; Rockwell, Sara ; Sartorelli, Alan C.
    Biochemical pharmacology v.51 no.12 ,pp. 1669 - 1678 , 1996 , 0006-2952 ,

    초록

    Abstract DT-Diaphorase catalyzes a two-electron reduction of mitomycin C (MC) and porfiromycin (POR) to reactive species. Many cell lines that overexpress DT-diaphorase and are sensitive to the mitomycins are protected from the aerobic cytotoxicity of these drugs by the DT-diaphorase inhibitor dicumarol. The cytoprotective properties of this relatively non-specific inhibitor, however, vanish under hypoxic conditions. To ascertain the role of DT-diaphorase in mitomycin bioactivation and cytotoxicity in living cells, a rat liver DT-diaphorase cDNA was transfected into Chinese hamster ovary cells. MC was equitoxic to the parental cells under oxygenated and hypoxic conditions. In contrast, POR was less toxic than MC to these cells under aerobic conditions, but significantly more toxic than MC under hypoxia. Two DT-diaphorase-transfected clones displayed increases in DT-diaphorase activity of 126- and 133-fold over parental cells. The activities of other oxidoreductases implicated in mitomycin bioreduction were unchanged. MC was more toxic to both DT-diaphorase-transfected lines than to parental cells; the toxicity of MC to the transfected lines was similar in air and hypoxia. POR was also more toxic to the DT-diaphorase-elevated clones than to parental cells under oxygenated conditions. Under hypoxia, however, the toxicity of POR to the transfected clones was unchanged from that of parental cells. The findings implicate DT-diaphorase in mitomycin bioactivation in living cells, but suggest that this enzyme does not contribute to the differential toxicity of MC or POR in air and hypoxia.

    원문보기

    원문보기
    무료다운로드 유료다운로드

    회원님의 원문열람 권한에 따라 열람이 불가능 할 수 있으며 권한이 없는 경우 해당 사이트의 정책에 따라 회원가입 및 유료구매가 필요할 수 있습니다.이동하는 사이트에서의 모든 정보이용은 NDSL과 무관합니다.

    NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니담기를 통하여 원문복사서비스 이용이 가능합니다.

    이미지

    Fig. 1 이미지

논문관련 이미지