Tyrosine kinase inhibitors (TKIs) are small molecules for the targeted treatment of cancer
cells. After ingestion, TKIs are excreted via faeces and urine into aquatic environment and
have potential adverse effects on non-target organisms. In the thesis we investigated the
cytotoxic and genotoxic activity of six TKIs: erlotinib (ERL), sorafenib (SOR), regorafenib
(REG), dasatinib (DAS), imatinib mesylate (IM) and nilotinib (NIL) on an in vitro model
of zebrafish liver cell line (Danio rerio; ZFL cells). Cytotoxicity was investigated by
staining of cells with propidium iodide and flow cytometry, effect on the cell cycle by
staining with Hoechst 33342 and flow cytometry, and effect on genomic stability by two
variants of micronucleus test; micronucleus test with flow cytometry and cytokinesis-block
micronucleus (CBMN) assay. ZFL cells were exposed to TKIs for 72 hours at different
concentrations of individual TKI in all experiments. In the CBMN assay, which confirmed
the results obtained by flow cytometry micronucleus assay, cells were exposed to TKIs at
only one concentration. The results showed that certain TKIs, namely SOR (4 µM), DAS
(0.015, 0.03, and 0.06 µM) and NIL (5, 10, and 20 µM), significantly influenced the
viability of ZFL cells. After 72 hours of exposure, TKIs did not significantly affect the cell
cycle of ZFL cells as well as the genomic stability of ZFL cells under exposure conditions.
The latter were also confirmed by the classical method of CBMN assay. None of the
studied TKIs had a significant effect on the number of micronuclei, nucleoplasmic bridges,
and nuclear buds, while the nuclear division index was significantly influenced by SOR (4
µM), REG (3 µM) and NIL (20 µM).
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