magistrsko delo
Slaven Drljača (Author), Metka Filipič (Reviewer), Darja Žgur-Bertok (Mentor), Darja Žgur-Bertok (Thesis defence commission member), Bojana Žegura (Thesis defence commission member), Metka Filipič (Thesis defence commission member), Damjana Drobne (Thesis defence commission member), Bojana Žegura (Co-mentor)

Abstract

Protirakava zdravila zaradi svojega genotoksičnega delovanja spadajo med najnevarnejše snovi, vendar je o njihovem pojavljanju v okolju in vplivih na okoljske organizme in zdravje ljudi malo znanega. Do sedaj so bili bolj ali manj spregledani predvsem zato, ker je uporaba in posledična okoljska izpostavljenost protirakavim zdravilom dosti manjša v primerjavi z drugimi zdravili. Raziskave zadnjih let namreč kažejo, da lahko ostanki zdravil v okolju resno ogrožajo tako organizme v okolju kot zdravje ljudi. Kljub temu podatki, ki jih imamo na voljo, ne zadostujejo za pripravo ustrezne ocene tveganja izpostavljenosti protirakavim zdravilom ter uvedbo ustreznih zaščitnih ukrepov. Zaradi omenjenih dejstev je bil cilj magistrske naloge določiti citotoksično in genotoksično delovanje štirih izbranih protirakavih zdravil z različnim načinom delovanja (5-fluorouracil, etopozid, cisplatin, in imatinib mezilat) na modelu ribjih jetrnih celic ZFL. Citotoksičnost smo ugotavljali s testom MTT, genotoksičnost pa s testom komet. Vsa izbrana protirakava zdravila so na celice ZFL delovala citotoksično v odvisnosti od časa in odmerka, pri čemer smo pri celicah izpostavljenih imatinibu opazili specifičen prag delovanja pri koncentraciji ~9.38 µg/mL pri vseh časih izpostavljenosti. S testom komet smo pokazali, da so vsa uporabljena protirakava zdravila pri necitotoksičnih odmerkih delovala genotoksično v odvisnosti od časa in odmerka. Malo je znanega o vplivu teh zdravil na vodne organizme; naši rezultati kažejo, da ZFL celice zagotavljajo pomembno in občutljivo orodje za pregled genotoksičnega potenciala okoljskih onesnaževalcev. Ocenjujemo, da so za natančnejšo opredelitev škodljivega delovanja protirakavih zdravil potrebne nadaljnje raziskave o njihovem citotoksičnem in genotoksičnem delovanju. Pri izvedbi magistrskega dela smo uporabili metodi, ki sta cenovno in časovno zelo primerne. Dobljeni rezultati so pokazali, da sta tudi dovolj občutljivi.

Keywords

cisplatin;test MTT;test komet;jetrne celice rib cebric;

Data

Language: Slovenian
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL BF - Biotechnical Faculty
Publisher: [S. Drljača]
UDC: 615.277(043.2)
COBISS: 4496719 Link will open in a new window
Views: 1186
Downloads: 614
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Other data

Secondary language: English
Secondary title: Cytotoxic and genotoxic effects selected cytostatics to fish liver cells in vitro
Secondary abstract: Cytostatics are among the most dangerous substances, but still not much is known on their occurrence in the environment and effects on environmental organisms and human. Until now, they have been more or less overlooked, mostly because their consumption and the consequent environmental exposure to cytostatics is much smaller compared to other drugs. Studies in recent years show that drug residues in the environment can pose a serious threat to organisms in the environment and human health. However, the available information is insufficient to assess appropriate risk assessment and introduce appropriate protective measures. Therefore, the aim of our work was to determine the cytotoxic and genotoxic effects of four selected cytotstatics with different modes of action (5-fluorouracil, etoposide, cisplatin and imatinib mesylate) in fish liver cells ZFL. Cytotoxicity was determined with the MTT assay, genotoxicity with the comet assay. All used cytostatics induced time- and dose-dependent cytotoxic effects in ZFL cells, while in the cells, exposed to imatinib mesylate, we observed a specific threshold dose response at a concentration ~ 9:38 mg / mL at all exposure times. With the comet assay we have shown that all the cytostatics were genotoxic in a time- and dose-dependent manner. Since not much is known on the effects of these drugs on aquatic organisms, our results suggest that ZFL cells provide an important and sensitive tool for the assessment of genotoxic potential of environmental contaminants. However, for a more indepth knowledge of their adverse effects further studies on their cytotoxic and genotoxic activity are needed. The methods used in our study are the cost- and time- effective, while our results demonstrate that they are sufficiently sensitive for this kind of research.
Secondary keywords: cisplatin;MTT assay;comet assay;zebrafish liver cells;
Type (COBISS): Master's thesis/paper
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. Ljubljana, Biotehniška fak.
Pages: IX, 52, [1] f.
ID: 10910421