20.500.12556/DiRROS-19323 Lethal and sub-lethal effects and modulation of gene expression induced by T kinase inhibitors in zebrafish (Danio Rerio) embryos 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. aquatic toxicity tyrosine kinase inhibitors zebrafish embryo toxicity test gene expression environmental hazard letalni in sub-letalni učinki ribe cebrice (Danio rerio) tirozin kinazni inhibitorji uravnavanje izražanja genov true false true Angleški jezik Slovenski jezik Neznano 2024-07-16 03:42:06 2024-07-16 05:04:36 2024-07-17 03:59:11 0000-00-00 00:00:00 2022 0 0 Nasl. z nasl. zaslona; Opis vira z dne 6. 1. 2022; Članek št. 4; str. 1-14 iss. 1 Vol. 10 Jan. 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2022-01-01 574.1:556:502/504 2305-6304 10.3390/toxics10010004 92898051 https://www.mdpi.com/2305-6304/10/1/4 1 9c7c8fcc-4314-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26647 RAZ_Elersek_Tina_2022.pdf RAZ_Elersek_Tina_2022.pdf 1 CCA2617F56FBC4A8B8450361B3974388 594972440e3bedcd3a2cdb16e220cc7b59564c857c4f57554dcca9bd40a2b96e 5c985a31-4320-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26679 Nacionalni inštitut za biologijo 0 0 0