{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:36:11Z","timestamp":1764646571815,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"strategic funding given to CIIMAR","award":["UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"Environmental Contamination and Toxicology Master\u2019s Degree (U.Porto)","award":["UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020","UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Polycyclic aromatic hydrocarbons (PAHs) and global warming impact aquatic ecosystems, eventually interacting. Monolayer (2D) cultures of cell lines, such as the rainbow trout liver RTL-W1, are employed for unveiling toxicological effects in fish. Nonetheless, three-dimensional (3D) models constitute an alternate paradigm, better emulating in vivo responses. Here, ultra-low attachment (ULA) plates were used to generate ten-day-old RTL-W1 spheroids for exposure to a control, a solvent control (0.1% DMSO) and the model PAH benzo[k]fluoranthene (BkF) at 10 and 100 nM and at 18 and 23 \u00b0C (thermal stress). After a 4-day exposure, spheroids were analyzed for viability (alamarBlue and lactate dehydrogenase), biometry (area, diameter and sphericity), histocytology (optical and electron microscopy), and mRNA levels of the detoxification-related genes cytochrome P450 (CYP)1A, CYP3A27, aryl hydrocarbon receptor (AhR), glutathione S-transferase (GST), uridine diphosphate\u2013glucuronosyltransferase (UGT), catalase (CAT), multidrug resistance-associated protein 2 (MRP2) and bile salt export protein (BSEP). Immunocytochemistry (ICC) was used to assess CYP1A protein expression. Neither temperature nor BkF exposure altered the spheroids\u2019 viability or biometry. BkF modified the cell\u2019s ultrastructure. The expression of CYP1A was augmented with both BkF concentrations, while AhR\u2019s increased at the higher concentration. The CYP1A protein showed a dose-dependent increase. Temperature and BkF concurrently modelled UGT\u2019s expression, which increased in the 100 nM condition at 23 \u00b0C. Conversely, CYP3A27, MRP2, and BSEP expressions lowered at 23 \u00b0C. CAT and GST mRNA levels were uninfluenced by either stressor. Overall, BkF and temperature impacted independently or interactively in RTL-W1 spheroids. These seem to be useful novel tools for studying the liver-related effects of temperature and PAHs.<\/jats:p>","DOI":"10.3390\/toxics13040302","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T04:42:07Z","timestamp":1744605727000},"page":"302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Benzo[k]fluoranthene at Two Temperatures on Viability, Structure, and Detoxification-Related Genes in Rainbow Trout RTL-W1 Cell Spheroids"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2530-6616","authenticated-orcid":false,"given":"Telma","family":"Esteves","sequence":"first","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-5358","authenticated-orcid":false,"given":"Fernanda","family":"Malh\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-4389","authenticated-orcid":false,"given":"Eduardo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-6507","authenticated-orcid":false,"given":"C\u00e9lia","family":"Lopes","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre of Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leix\u00f5es, Av. General Norton de Matos s\/n, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6192","DOI":"10.1038\/s41467-024-49863-0","article-title":"Achieving net zero greenhouse gas emissions critical to limit climate tipping risks","volume":"15","author":"Schleussner","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_2","unstructured":"M\u00e9ndez, C., Simpson, N., Johnson, F., and Birt, A. (2023). 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