|
|
|
|
| LEADER |
07820cam a2200505 i 4500 |
| 001 |
NSK01000172772 |
| 003 |
HR-ZaNSK |
| 005 |
20080605100400.0 |
| 008 |
960923s1995 ci a m 000 0 hrv |
| 035 |
|
|
|9 (HR-ZaNSK)172974
|
| 035 |
|
|
|9 (HR-ZaNSK)960923021
|
| 035 |
|
|
|a (HR-ZaNSK)000172772
|
| 040 |
|
|
|a HR-ZaNSK
|b hrv
|c HR-ZaNSK
|e ppiak
|
| 041 |
0 |
|
|a hrv
|
| 044 |
|
|
|a ci
|c hr
|
| 080 |
|
|
|a 574.5:615.9
|
| 080 |
|
|
|a 504.746.08
|
| 100 |
1 |
|
|a Pivčević, Branka
|
| 245 |
1 |
0 |
|a Mjerenje inhibitora mehanizma multiksenobiotičke otpornosti u vodenom okolišu :
|b doktorska disertacija /
|c Branka Pivčević.
|
| 260 |
|
|
|a Zagreb :
|b B. Pivčević,
|c 1995.
|e ([s. l. :
|f s. n.])
|
| 300 |
|
|
|a 97 str. :
|b table, ilustr., graf. prikazi ;
|c 30 cm.
|
| 500 |
|
|
|a Doktor prirodnih znanosti - biologija
|
| 500 |
|
|
|a Mentor: Branko Kurelec; Komisija za ocjenu: Maja Osmak, Branko Kurelec, Oskar Springer; Komisija za obranu: Maja Osmak, Branko Kurelec, Oskar Springer; datum obrane: 12.07.1995; datum promocije: 01.12.1995.
|
| 502 |
|
|
|a Sveučilište u Zagrebu, Institut "Ruđer Bošković", Zagreb, 1995
|
| 504 |
|
|
|a Bibliografija: str. 83-93
|
| 504 |
|
|
|a Summary
|
| 520 |
|
|
|a Sažetak: Svim do danas ispitanim vodenim organizmima svojstven je mehanizam istovremene otpornosti na više ksenobiotika (eng. multixenobiotic resistance, MXR), koji predstavlja dio prirodnog obrambenog sustava tih organizama za obranu od endogenih metabolita i ksenobiotika iz okoliša. Taj mehanizam, koristeći membranski P-glikoprotein, izbacuje iz stanice relativno hidrofobne tvari, sprečavajući njihovu akumulaciju u stanici. Neke tvari mogu inhibirati i blokirati djelovanje P-glikoproteinske pumpe. Takve tvari, nazvane MXR-inhibitori, ili kemosenzitizatori, same po sebi mogu biti i neotrovne, ali blokirajući MXR mehanizam mogu uzrokovati povećanu akumulaciju drugih otrovnih ksenobiotika, s mogućim patobiološkim posljedicama za vodeni organizam.
|
| 520 |
|
|
|a Tvari takvih svojstava očito spadaju među veoma opasna zagađivala, pa bi njihovu nazočnost u okolišu trebalo prepoznati i izmjeriti. Koristeći dvije modificirane metode, detektirali smo i kvantificirali MXR-inhibitore u XAD-7, Blue-cotton i heksanskim koncentratima/ekstraktima voda, XAD-7 koncentratima intersticijskih voda i DCM-M ekstraktima sedimenata, nezagađenih rijeka Odre, Dobre, Mrežnice i Korane, te zagađenih rijeka Save i Schwarzbach. Metodom vezanja (eng. binding) uspoređivali smo inhibitorni potencijal koncentrata/ekstrakta u vezanju 3H-VCR na membranske vezikle kore nadbubrežne žlijezde junca (referentni izvor P-glikoproteina), s inhibitornim učinkom 20 [mikro]M kemosenzitizatora verapamila.
|
| 520 |
|
|
|a Akumulacijskom verzijom metode na mikroploči uspoređivali smo inhibitorni potencijal koncentrata/ekstrakta na akumulaciju 3H-VCR u otpornim S180/dox stanicama s inhibitornim učinkom 20 [mikro]M verapamila. Objema se metodama pokazalo da XAD-7 smola izvlači više MXR-inhibitora iz vode od Blue-cotton-a i heksana. Metoda vezanja pokazala se nepogodna za istovremeno mjerenje velikog broja uzoraka, a zbog tehničke neprimjerenosti ekstrakata i za mjerenje MXR-inhibitora u uzorcima sedimenata. Koncentracija MXR-inhibitora izmjerena akumulacijskom verzijom najveća je u sedimentima, od 6,6 do 23,7 ppm, zatim u inersticijskim vodama, od 15,5 do 77,9 ppb, a najniža u vodama, od 1,1 do 6,8 ppb verapamilskih ekvivalenata.
|
| 520 |
|
|
|a Na temelju naših prijašnjih istraživanja, nađene koncentracije MXR-inhibitora u sedimentima u razini su djelatnih koncentracija (ppm-razina), za razliku od koncentracija MXR-inhibitora u vodi i intersticijskoj vodi koje su ispod djelatnih koncentracija(ppb-razina). Znakovito je međutim, da od dvije zagađene rijeke samo voda rijeke Schwarzbach sadrži veću koncentraciju MXR-inhibitora (33 ppb). Koncentracije MXR-inhibitora u intersticijskim vodama i sedimentima ne prate stupanj zagađenja rijeka, ali pokazuju značajne sezonske varijacije.
|
| 520 |
|
|
|a Daljnjim istraživanjima valjalo bi istražiti koje bi od ovih koncentracija mogle preobratiti otpornost vodenih organizama iz tih rijeka u patobiološku osjetljivost, odnosno koje bi koncentracije antropogenih MXR-kemosenzitizatora mogle imati takav ekotoksikološki značaj, koji bi nametnuo potrebu kontrole njihova odlaganja u okolišu.
|
| 520 |
|
|
|a Summary: All aquatic organisms investigated thus far, express a multixenobiotic resistance (MXR) mechanism, that represents a part of natural defense system against endogenous and environmental xenobiotics. This mechanism utilizes a membrane P-glycoprotein that extrudes relatively hydrophobic compounds out of the cell, preventing their intracellular accumulation. Activity of the P-glycoprotein pump can be inhibited, or blocked, by certain chemicals. These chemicals, called MXR-inhibitors, or chemosensitizers, cause accumulation of toxic xenobiotics, possibly with pathobiological consenquences for aquatic organisms. Compounds with such properties deserve a top rank among environmentaly hazardous chemicals. Their presence and concentration in the environment should be detected and measured.
|
| 520 |
|
|
|a Using two methods, we detected and quantified MXR-inhibitors in XAD-7-, Blue-cotton- and hexane-water concentrates/extracts, in XAD-7-interstitial water concentrates, and in DCM-M-sediment extracts of non-polluted Odra, Dobra, Mrežnica, Korana, and polluted Sava and Schwarzbach rivers. With the first method, the binding assay, we compared the inhibitory potential of concentrates/extracts on binding of 3H-VCR on membrane vesicles from cortex of male bovine adrenal gland (referent source of P-glycoprotein) with the inhibitory effect of 20 [mikro]M chemosensitizer verapamil. With the second method, an accumulation version of microplate method, we compared the inhibitory potential of concentrates/extracts on accumulation of 3H-VCR in resistant S180/dox cells with the inhibitory effect of 20 [mikro]M verapamil.
|
| 520 |
|
|
|a Both methods showed that XAD-7 resin draws out from water more MXR-inhibitors than Blue-cotton and hexane. The binding method showed to be inconvenient for simultaneous measurement of large number of samples, because of technical inadequacy of sediment extracts. Using the accumulation version, the concentration of MXR-inhibitors was found to be much higher in sediments, (6.6 to 23.7 ppm), than in interstitial water, (15.5 to 77.9 ppb), or in water, (1.1 to 6.8 ppb) of verapamil equivalents. According to our previous research, the concentrations of MXR-inhibitors found in sediments were effective (ppm-level), while concentrations of MXR-inhibitors in waters and interstitial waters were below the effective level (ppb-level).
|
| 520 |
|
|
|a It was interesting, however, that among two polluted rivers only the Schwarzbach river water contained a higher concentration of MXR-inhibitors (33 ppb). Concentration of MXR-inhibitors in interstitial waters and sediments were not in correlation with the state of pollution. They exerted, however, significant seasonal variations. Futher research should establish the threshold concentrations of MXR-inhibitors that can revert the natural resistance of aquatic organisms to pathobiological sensitiveness. If such concentrations of anthropogenic MXR-inhibitors are present in water ecosystem, regulatory environmental measures should be instituted.
|
| 650 |
|
7 |
|a Ksenobiotici
|x Ekotoksičnost
|2 nskps
|
| 650 |
|
7 |
|a Vodene životinje
|x Ksenobiotička otpornost
|2 nskps
|
| 700 |
1 |
|
|a Kurelec, Branko
|4 cns
|4 oth
|
| 700 |
1 |
|
|a Osmak, Maja
|4 oth
|
| 700 |
1 |
|
|a Springer, Oskar
|4 oth
|
| 981 |
|
|
|p CRO
|r HRB1995
|
| 998 |
|
|
|n DCD
|c rjki9803
|c rjkp9803
|c sbni9807
|
| 852 |
4 |
|
|j DCD-ZG-149/96
|
| 876 |
|
|
|e DCD
|a 149/1996
|
| 886 |
0 |
|
|2 unimarc
|b 07568iam0 2200433 450
|