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Lethal and sub-lethal effects and modulation of gene expression induced by T kinase inhibitors in zebrafish (Danio Rerio) embryos [Elektronski vir]Eleršek, Tina, 1976- ...: Tyrosine kinase inhibitors (TKIs) are designed for targeted cancer therapy. The consumption of these drugs during the last 20 years has been constantly rising. In the zebrafish (Danio rerio) embryo ... toxicity test, we assessed the toxicity of six TKIs: imatinib mesylate, erlotinib, nilotinib, dasatinib, sorafenib and regorafenib. Imatinib mesylate and dasatinib induced lethal effects, while regorafenib, sorfenib and dasatinib caused a significant increase of sub-lethal effects, predominantly oedema, no blood circulation and formation of blood aggregates. The analyses of the changes in the expression of selected genes associated with the hormone system after the exposure to imatinib mesylate, dasatinib and regorafenib demonstrated that all three tested TKIs deregulated the expression of oestrogen receptor esr1, cytochrome P450 aromatase (cypa19b) and hydroxysteroid-dehydrogenase (hsd3b), regorafenib, and also thyroglobulin (tg). The expression of genes involved in the DNA damage response (gadd45 and mcm6) and apoptosis (bcl2) was deregulated only by exposure to regorafenib. The data indicate that common mechanisms, namely antiangiogenic activity and interference with steroidogenesis are involved in the TKI induced sub-lethal effects and potential hormone disrupting activity, respectively. The residues of TKIs may represent an environmental hazard; therefore, further ecotoxicological studies focusing also on the effects of their mixtures are warranted.Source: Toxics : Elektronski vir. - ISSN 2305-6304 (Vol. 10, iss. 1, Jan. 2022, str. 1-14)Type of material - e-article ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 92898051
Author
Eleršek, Tina, 1976- |
Novak, Matjaž, biologija, 1987- |
Mlinar, Mateja, biologinja |
Virant, Igor, 1979- |
Bahor, Nika |
Leben, Karin |
Žegura, Bojana |
Filipič, Metka, 1954-
Topics
letalni in sub-letalni učinki |
ribe cebrice (Danio rerio) |
tirozin kinazni inhibitorji |
uravnavanje izražanja genov |
aquatic toxicity |
tyrosine kinase inhibitors |
zebrafish embryo toxicity test |
gene expression |
environmental hazard
Shelf entry
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Eleršek, Tina, 1976- | 22616 |
Novak, Matjaž, biologija, 1987- | 34200 |
Mlinar, Mateja, biologinja | 39755 |
Virant, Igor, 1979- | 35763 |
Bahor, Nika | |
Leben, Karin | |
Žegura, Bojana | 20767 |
Filipič, Metka, 1954- | 09892 |
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