@article {varga_cytotoxicity_2024,
	title = {Cytotoxicity of Prymnesium parvum extracts and prymnesin analogs on epithelial fish gill cells RTgill-W1 and the human colon cell line HCEC-1CT},
	journal = {Archives of Toxicology},
	year = {2024},
	month = {jan},
	abstract = {Harmful algal blooms kill fish populations worldwide, as exemplified by the haptophyte microalga Prymnesium~parvum. The suspected causative agents are prymnesins, categorized as A-, B-, and C-types based on backbone carbon atoms. Impacts of P.~parvum extracts and purified prymnesins were tested on the epithelial rainbow trout fish gill cell line RTgill-W1 and on the human colon epithelial cells HCEC-1CT. Cytotoxic potencies ranked A > C > B-type with concentrations spanning from low (A- and C-type) to middle (B-type) nM ranges. Although RTgill-W1 cells were about twofold more sensitive than HCEC-1CT, the cytotoxicity of prymnesins is not limited to fish gills. Both cell lines responded rapidly to prymnesins; with EC50 values for B-types in RTgill-W1 cells of 110 {\textpm} 11~nM and 41.5 {\textpm} 0.6~nM after incubations times of 3 and 24~h. Results of fluorescence imaging and measured lytic effects suggest plasma membrane interactions. Postulating an osmotic imbalance as mechanisms of toxicity, incubations with prymnesins in media lacking either Cl-, Na+, or Ca2+ were performed. Cl- removal reduced morphometric rearrangements observed in RTgill-W1 and cytotoxicity in HCEC-1CT cells. Ca2+-free medium in RTgill-W1 cells exacerbated effects on the cell nuclei. Prymnesin composition of different P.~parvum strains showed that analog composition within one type scarcely influenced the cytotoxic potential, while analog type potentially dictate potency. Overall, A-type prymnesins were the most potent ones in both cell lines followed by the C-types, and lastly B-types. Disturbance of Ca2+ and Cl- ionoregulation may be integral to prymnesin toxicity.},
	keywords = {Fluorescence microscopy, Ichthyotoxin, Ionoregulation, Microalgae, MS, RCC1436, RCC191, UHPLC},
	issn = {1432-0738},
	doi = {10.1007/s00204-023-03663-5},
	url = {https://doi.org/10.1007/s00204-023-03663-5},
	author = {Varga, Elisabeth and Prause, H{\'e}l{\`e}ne-Christine and Riepl, Matthias and Hochmayr, Nadine and Berk, Deniz and Attakpah, Eva and Kiss, Endre and Medi{\'c}, Nikola and Del Favero, Giorgia and Larsen, Thomas Ostenfeld and Hansen, Per Juel and Marko, Doris}
}
