Genotoksični učinak irinotekana na ljudske tumorske stanice jetre i crijeva

master's thesis

• Title (english): Genotoxic effect of irinotecanon human liver and colon tumor cells
• Author: Lejla Joukhadar
• Mentor: Ksenija Durgo (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biology and Microbial Genetics); Zagreb
• Defense date and country: 2018-10-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Food Technology

Abstract

Od ukupnog broja svih godišnje dijagnosticiranih karcinoma u svijetu, karcinomi probavnog sustava su na vodećoj poziciji. Među njima najvišu pojavnost ima kolorektalni karcinom, što ga svrstava među vodeće zdravstvene probleme kako u svijetu tako i u Hrvatskoj. Irinotekan (CPT-11) je polusintetski analog kamptotecina (CPT) koji je glavni lijek izbora u terapiji metastatskog kolorektalnog karcinoma. Cilj ovog rada je istražiti citotoksičnost, genotoksičnost i svojstvo indukcije slobodnih radikala različitih koncentracija irinotekana. Kao test sustavi korištene su humana stanična linija hepatocelularnog karcinoma jetre (HepG2) i humana stanična linija adenokarcinoma epitela debelog crijeva (Caco-2) koje su bile izložene djelovanju irinotekana tijekom 2, 4, 24 i 48 sati. Dokazano je da irinotekan djeluje toksično produljenjem vremena tretmana na obje stanične linije. Na stanicama jetre toksičnost raste u ovisnosti o koncentraciji, dok na stanicama crijeva ovisnost o kocentraciji nije dokazana. Također je uočena povezanost citotoksičnog učinka irinotekana s indukcijom slobodnih radikala. S produljenjem vremena inkubacije dolazi do genotoksičnog učinka irinotekana na obje tretirane stanične linije.

Abstract (english)

Of the total number of all yearly diagnosed carcinomas in the world, cancers that affect the digestive system are in a leading position. Among them, the highest incidence is colorectal cancer, which puts it among the leading health problems in the world as well as in Croatia. Irinotecan (CPT-11) is a semi-synthetic analogue of camptothecin (CPT) which is the major drug in the choice of metastatic colorectal cancer therapy. The aim of this work is to investigate the cytotoxicity, genotoxicity and induction of free radicals of different concentrations of irinotecan. As the test system the human hepatocellular carcinoma cell line (HepG2) and the human colon adenocarcinoma cell line (Caco-2) were exposed to irinotecan during 2, 4, 24, and 48 hours. Results have shown that irinotecan cytotoxicity is dependent on the cell line. In liver cells, toxicity is increasing depending on concentrations, while on the colon cells no dependence on the concentration has been demonstrated. Also, the association of cytotoxic effect of irinotecan with the induction of free radicals was observed. With the prolongation of incubation time, the genotoxic effect of irinotecan on both treated cell lines is reached.

• Keywords: Irinotekan; citotoksičnost; indukcija slobodnih radikala; genotoksičnost; stanične linije HepG2 i Caco-2; in vitro testovi
• Keywords (english): Irinotecan; cytotoxicity; induction of free radicals; genotoxicity; HepG2 and Caco-2 cell lines; in vitro assays
• Language: croatian
• URN:NBN: urn:nbn:hr:159:887469
• Study programme: Title: Food Safety Management; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka upravljanja sigurnošću hrane (magistar/magistra inženjer/inženjerka upravljanja sigurnošću hrane)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-12-04 11:10:20